Type I Collagen (type + i_collagen)

Distribution by Scientific Domains
Distribution within Medical Sciences

Terms modified by Type I Collagen

  • type i collagen expression
  • type i collagen gel
  • type i collagen mrna

  • Selected Abstracts


    Regional Alterations of Type I Collagen in Rat Tibia Induced by Skeletal Unloading,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2002
    Masashi Shiiba
    Abstract Skeletal unloading induces loss of mineral density in weight-bearing bones that leads to inferior bone mechanical strength. This appears to be caused by a failure of bone formation; however, its mechanisms still are not well understood. The objective of this study was to characterize collagen, the predominant matrix protein in bone, in various regions of tibia of rats that were subjected to skeletal unloading by 4 weeks tail suspension. Sixteen male Sprague-Dawley rats (4 months old) were divided into tail suspension and ambulatory controls (eight rats each). After the tail suspension, tibias from each animal were collected and divided into five regions and collagen was analyzed. The collagen cross-linking and the extent of lysine (Lys) hydroxylation in unloaded bones were significantly altered in proximal epiphysis, diaphysis, and, in particular, proximal metaphysis but not in distal regions. The pool of immature/nonmineralized collagen measured by its extractability with a chaotropic solvent was significantly increased in proximal metaphysis. These results suggest that skeletal unloading induced an accumulation of post-translationally altered nonmineralized collagen and that these changes are bone region specific. These alterations might be caused by impaired osteoblastic function/differentiation resulting in a mineralization defect. [source]


    Changes in gene expression of individual matrix metalloproteinases differ in response to mechanical unloading of tendon fascicles in explant culture

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 10 2008
    Diane R. Leigh
    Abstract Immobilization of the tendon and ligament has been shown to result in a rapid and significant decrease in material properties. It has been proposed that tissue degradation leading to tendon rupture or pain in humans may also be linked to mechanical unloading following focal tendon injury. Hence, understanding the remodeling mechanism associated with mechanical unloading has relevance for the human conditions of immobilization (e.g., casting), delayed repair of tendon ruptures, and potentially overuse injuries as well. This is the first study to investigate the time course of gene expression changes associated with tissue harvest and mechanical unloading culture in an explant model. Rat tail tendon fascicles were harvested and placed in culture unloaded for up to 48 h and then evaluated using qRT-PCR for changes in two anabolic and four catabolic genes at 12 time points. Our data demonstrates that Type I Collagen, Decorin, Cathepsin K, and MMP2 gene expression are relatively insensitive to unloaded culture conditions. However, changes in both MMP3 and MMP13 gene expression are rapid, dramatic, sustained, and changing during at least the first 48 h of unloaded culture. This data will help to further elucidate the mechanism for the loss of mechanical properties associated with mechanical unloading in tendon. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1306,1312, 2008 [source]


    Human primary corneal fibroblasts synthesize and deposit proteoglycans in long-term 3-D cultures

    DEVELOPMENTAL DYNAMICS, Issue 10 2008
    R. Ren
    Abstract Our goal was to develop a 3-D multi-cellular construct using primary human corneal fibroblasts cultured on a disorganized collagen substrate in a scaffold-free environment and to use it to determine the regulation of proteoglycans over an extended period of time (11 weeks). Electron micrographs revealed multi-layered constructs with cells present in between alternating parallel and perpendicular arrays of fibrils. Type I collagen increased 2,4-fold. Stromal proteoglycans including lumican, syndecan4, decorin, biglycan, mimecan, and perlecan were expressed. The presence of glycosaminoglycan chains was demonstrated for a subset of the core proteins (lumican, biglycan, and decorin) using lyase digestion. Cuprolinic blue,stained cultures showed that sulfated proteoglycans were present throughout the construct and most prominent in its mid-region. The size of the Cuprolinic-positive filaments resembled those previously reported in a human corneal stroma. Under the current culture conditions, the cells mimic a development or nonfibrotic repair phenotype. Developmental Dynamics 237:2705,2715, 2008. © 2008 Wiley-Liss, Inc. [source]


    Type I collagen is a genetic modifier of matrix metalloproteinase 2 in murine skeletal development

    DEVELOPMENTAL DYNAMICS, Issue 6 2007
    Mikala Egeblad
    Abstract Recessive inactivating mutations in human matrix metalloproteinase 2 (MMP2, gelatinase A) are associated with syndromes that include abnormal facial appearance, short stature, and severe bone loss. Mmp2,/, mice have only mild aspects of these abnormalities, suggesting that MMP2 function is redundant during skeletal development in the mouse. Here, we report that Mmp2,/, mice with additional mutations that render type I collagen resistant to collagenase-mediated cleavage to TCA and TCB fragments (Col1a1r/r mice) have severe developmental defects resembling those observed in MMP2 -null humans. Composite Mmp2,/,;Col1a1r/r mice were born in expected Mendelian ratios but were half the size of wild-type, Mmp2,/,, and Col1a1r/r mice and failed to thrive. Furthermore, composite Mmp2,/,;Col1a1r/r animals had very abnormal craniofacial features with shorter snouts, bulging skulls, incompletely developed calvarial bones and unclosed cranial sutures. In addition, trabecular bone mass was reduced concomitant with increased numbers of bone-resorbing osteoclasts and osteopenia. In vitro, MMP2 had a unique ability among the collagenolytic MMPs to degrade mutant collagen, offering a possible explanation for the genetic interaction between Mmp2 and Col1a1r. Thus, because mutations in the type I collagen gene alter the phenotype of mice with null mutations in Mmp2, we conclude that type I collagen is an important modifier gene for Mmp2. Developmental Dynamics 236:1683,1693, 2007. © 2007 Wiley-Liss, Inc. [source]


    The hip joint: the fibrillar collagens associated with development and ageing in the rabbit

    JOURNAL OF ANATOMY, Issue 1 2001
    YVETTE S. BLAND
    The fibrillar collagens associated with the articular cartilages, joint capsule and ligamentum teres of the rabbit hip joint were characterised from the 17 d fetus to the 2-y-old adult by immunohistochemical methods. Initially the putative articular cartilage contains types I, III and V collagens, but when cavitation is complete in the 25 d fetus, type II collagen appears. In the 17 d fetus, the cells of the chondrogenous layers express type I collagen mRNA, but not that of type II collagen. Types III and V collagens are present throughout life, particularly pericellularly. Type I collagen is lost. In all respects, the articular cartilage of the hip joint is similar to that of the knee. The joint capsule contains types I, III and V collagens. In the fetus the ligamentum teres contains types I and V collagens and the cells express type I collagen mRNA; type III collagen is confined mainly to its surface and insertions. After birth, the same distribution remains, but there is more type III collagen in the ligament, proper. The attachment to the cartilage of the head of the femur is marked only by fibres of type I collagen traversing the cartilage; the attachment cannot be distinguished in preparations localising types III and V collagens. The attachment to the bone at the lip of the acetabulum is via fibres of types I and V collagens and little type III is present. The ligament is covered by a sheath of types III and V collagens. Type II collagen was not located in any part of the ligamentum teres. The distribution of collagens in the ligamentum teres is similar to that in the collateral ligaments of the knee. Its insertions are unusual because no fibrocartilage was detected. [source]


    Preparation and characterization of complex gel of type I collagen and aluminosilicate containing imogolite nanofibers

    JOURNAL OF APPLIED POLYMER SCIENCE, Issue 4 2010
    Asuka Nakano
    Abstract Complex gel materials of Type I collagen and aluminosilicate containing imogolite nanofibers were prepared as opaque gel by mixing an acidic fine dispersion of aluminosilicate with an acidic solution of collagen. The product was stained blue by Coomassie Brilliant Blue (CBB), indicating that the gel contained collagen. A white sponge was obtained after lyophilization of the complex gel. Elemental analysis revealed that the complex contains C, H, N, Al, and Si atoms; and the compositional ratio of aluminosilicate/collagen (w/w) was calculated as 0.75 for the complex gel when aluminosilicate was mixed with an equal quantity of collagen. Transmission electron microscope (TEM) observation showed that aluminosilicate nanofibers were homogeneously distributed in the collagen matrix. The thermogravimetric analysis (TGA) curve of the complex was not a simple summation of each components, and especially, the weight loss step corresponding to detachment of the adsorbed water observed in aluminosilicate became difficult to distinguish, suggesting that the adsorbed water was removed in the complexation. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 [source]


    Modeling of Bovine Type-I Collagen Fibrils: Interaction with Pickling and Retanning Agents

    MACROMOLECULAR BIOSCIENCE, Issue 2 2007
    Rosa E. Bulo
    Abstract Bovine Type I collagen was investigated, building on a large scale computer model of a collagen fibril in water, and focusing on two stages of the leather manufacturing process. The effects of different salts (NaCl, CaCl2, and Na2SO4) on the swelling behavior of collagen at low pH (the pickling process) were studied. The salts suppress the swelling of the fibrils at low pH and we find specific stabilizing influences for CaCl2 and Na2SO4, due to weak Ca2+/Cl, and strong SO/lysine/arginine interactions, respectively. Using state-of-the-art sampling techniques, such as the metadynamics algorithm, to allow an efficient exploration of configuration space, we were able to investigate the effect of polyacrylate and poly(methyl acrylate) , two polymeric retanning agents , on the fibril. Both polymers interact with the ammonium groups on the surface, but polyacrylate shows significantly stronger interactions. We suggest that it is this stronger interaction that contributes to the reduced suitability of PAA as a tanning agent. [source]


    Effects of interleukin 18 on injury and activation of human proximal tubular epithelial cells

    NEPHROLOGY, Issue 1 2007
    DONG LIANG
    SUMMARY: Background/Aims: Injury and activation of tubular proximal epithelial cells (TEC) play central roles in renal tubulointerstitial fibrosis (TIF), but its mechanisms remain obscure. Interleukin 18 (IL-18) is overproduced during chronic kidney diseases (CKD), but how IL-18 affects the biological behaviour of TEC is not clear. The aim of the present study is to reveal the role of IL-18 in renal TIF. Methods: The expressions of IL-18 and IL-18 receptor in TEC were detected by immunohistochemical staining in vivo and by reverse transcriptase polymerase chain reaction (RT-PCR) in vitro. TEC line (HK-2 cells) were incubated without or with IL-18. Cell proliferation and cell cycle were evaluated by methyl thiazolyl tetrazolium assay and flow cytometric analysis, respectively. Cell apoptosis was assessed by Hoechst 33258 staining. Expression of ,-smooth muscle actin was evaluated by RT-PCR, immunocytochemical staining and flow cytometric analysis, respectively. Type I collagen, fibronectin, MCP-1 and RANTES in cultured supernatants were measured by enzyme-linked immunosorbent assay. Results: IL-18 expression in TEC increased significantly in CKD state. IL-18 receptor was constitutively expressed in normal proximal TEC, and its expression increased strongly in CKD state. Proliferation and cell cycle of HK-2 cells were not affected by IL-18. Cell apoptosis, ,-smooth muscle actin expression, type I collagen and fibronectin production as well as MCP-1 secretion were promoted by IL-18 in dosage- and/or time-dependent manners, but RANTES secretion was not affected. Conclusion: IL-18 may play a crucial role in the process of TIF by promoting TEC injury and activation, and could be a target of the therapeutic approaches against TIF. [source]


    The Response of Articular Chondrocytes to Type II Collagen,Au Nanocomposites

    ARTIFICIAL ORGANS, Issue 12 2007
    Shan-hui Hsu
    Abstract:, The nanocomposites (denoted "CII,Au") of porcine type II collagen (CII) with 0.05, 0.1, 0.5, 1, or 2.5% (wt/wt) Au nanoparticles (,5 nm) were fabricated for potential use in cartilage tissue engineering. Au formed clusters on the surface of all nanocomposites and appeared to distribute along the collagen fibrils inside the matrix. The addition of Au at low concentrations (,0.5%) increased the modulus and viscosity, as well as the free radical-scavenging ability. These effects decreased at higher concentrations of Au. The chondrocytes on CII,Au became spindle-like with lamellipodia formation. Cell proliferation on CII,Au 0.1% was promoted. Nitric oxide (NO) in the culture medium was reduced by CII,Au 0.05% and CII,Au 0.1%. Type I collagen, aggrecan, and Sox 9 gene expressions increased with an increased Au content, but slightly decreased at 2.5% Au. There was no significant difference in the CII gene expression. The cellular uptake of Au was observed but less than that which occurred when 10 ppm of Au was added in culture medium. Chondrocytes cultured with ,10 ppm of Au nanoparticles showed neither cytotoxicity nor change in gene expression. Au at an appropriate amount could be well dispersed in CII, and enhanced the material modulus, antioxidant effect, as well as the chondrocyte growth and matrix production. [source]


    Differential Long-Term Stimulation of Type I versus Type III Collagen After Infrared Irradiation

    DERMATOLOGIC SURGERY, Issue 7 2009
    YOHEI TANAKA MD
    BACKGROUND The dermis is composed primarily of type I (soft) and type III (rigid scar-like) collagen. Collagen degradation is considered the primary cause of skin aging. Studies have proved the efficacy of infrared irradiation on collagen stimulation but have not investigated the differential long-term effects of infrared irradiation on type I and type III collagen. OBJECTIVE To determine differential long-term stimulation of type I and type III collagen after infrared (1,100,1,800 nm) irradiation. METHODS AND MATERIALS In vivo rat tissue was irradiated using the infrared device. Histology samples were analyzed for type I and III collagen stimulation, visual changes from baseline, and treatment safety up to 90 days post-treatment. RESULTS Infrared irradiation provided long-term stimulation of type I collagen and temporary stimulation of type III collagen. Treatment also created long-term smoothing of the epidermis, with no observed complications. CONCLUSIONS Infrared irradiation provides safe, consistent, long-term stimulation of type I collagen but only short-term stimulation in the more rigid type III collagen. This is preferential for cosmetic patients looking for improvement in laxity and wrinkles while seeking smoother, more youthful skin. [source]


    Type I collagen is a genetic modifier of matrix metalloproteinase 2 in murine skeletal development

    DEVELOPMENTAL DYNAMICS, Issue 6 2007
    Mikala Egeblad
    Abstract Recessive inactivating mutations in human matrix metalloproteinase 2 (MMP2, gelatinase A) are associated with syndromes that include abnormal facial appearance, short stature, and severe bone loss. Mmp2,/, mice have only mild aspects of these abnormalities, suggesting that MMP2 function is redundant during skeletal development in the mouse. Here, we report that Mmp2,/, mice with additional mutations that render type I collagen resistant to collagenase-mediated cleavage to TCA and TCB fragments (Col1a1r/r mice) have severe developmental defects resembling those observed in MMP2 -null humans. Composite Mmp2,/,;Col1a1r/r mice were born in expected Mendelian ratios but were half the size of wild-type, Mmp2,/,, and Col1a1r/r mice and failed to thrive. Furthermore, composite Mmp2,/,;Col1a1r/r animals had very abnormal craniofacial features with shorter snouts, bulging skulls, incompletely developed calvarial bones and unclosed cranial sutures. In addition, trabecular bone mass was reduced concomitant with increased numbers of bone-resorbing osteoclasts and osteopenia. In vitro, MMP2 had a unique ability among the collagenolytic MMPs to degrade mutant collagen, offering a possible explanation for the genetic interaction between Mmp2 and Col1a1r. Thus, because mutations in the type I collagen gene alter the phenotype of mice with null mutations in Mmp2, we conclude that type I collagen is an important modifier gene for Mmp2. Developmental Dynamics 236:1683,1693, 2007. © 2007 Wiley-Liss, Inc. [source]


    Type I collagen markers in cord serum of appropriate vs. small for gestational age infants born during the second half of pregnancy

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2001
    T. Saarela
    Background The serum concentration of the N-terminal propeptide of type I procollagen (PINP) reflects the synthesis rate of type I collagen, whereas the corresponding C-terminal telopeptide (ICTP) mirrors its degradation. Design PINP and ICTP were measured in a total of 690 cord serum samples from 592 appropriate-for-gestational-age (AGA) infants and 98 smal-for-gestational-age (SGA) infants. These markers were compared between AGA and SGA infants of different gestational ages, ranging from 23 to 41 weeks, and birth weights, from 620 to 4555 g. Results Both PINP and ICTP levels were very high in the preterm AGA infants and declined significantly with advancing gestational age, paralleling the shape of the fetal growth velocity curve. Regardless of the quite large interindividual variations observed in these markers, PINP was significantly lower in both the preterm and term AGA infants than in the SGA infants. This was also the case for ICTP in the preterm infants of gestational age less than 36 weeks. In stepwise multiple regression analyses, gestational age, being either AGA or SGA and head circumference were significant factors to explain the levels of PINP and ICTP. The levels of PINP and ICTP were correlated with each other highly significantly in both the AGA and SGA infants (rs = 0·700 and 0·692, respectively; P < 0·001 in both). Conclusions The levels of type I collagen markers seem to follow closely the shape of the fetal growth velocity curve during different stages of gestation. However, because of the large interindividual variations observed, further studies are needed before the significance of these markers for the assessment of normal and abnormal fetal growth can be established. [source]


    Bone turnover markers and sex hormones in men with idiopathic osteoporosis

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2001
    P. Pietschmann
    Background In contrast to osteoporosis in postmenopausal women, osteoporosis in men has received much less attention. Patients and We determined various biochemical parameters of bone metabolism and sex hormones in 31 men with idiopathic osteoporosis and 35 age matched control subjects. Results In the men with osteoporosis, a significantly increased urinary excretion of deoxypyridinoline (5·3 ± 0·2 vs. 4·6 ± 0·2 nmol mmol,1 creatinine; P = 0·033) in addition to increased serum levels of the c-terminal telopeptide of type I collagen (2677 ± 230 vs. 2058 ± 153 pmol; P = 0·037) were found. While parameters of bone formation were not significantly different in the patients and controls, serum bone sialoprotein levels were significantly decreased in the patients (3·7 ± 0·8 vs. 12·4 ± 4·0 ng mL,1; P = 0·021). Moreover, in men with idiopathic osteoporosis, lower levels of estradiol (91·3 ± 5·8 vs. 114·6 ± 7·8 pmol L,1; P = 0·044), higher levels of sex hormone binding globulin (31·5 ± 3·1 vs. 24·2 ± 1·4 nmol L,1; P = 0·034) and a decreased free androgen index (42·6 ± 5·2 vs. 56·4 ± 5·9; P = 0·016) were seen. Serum estradiol levels correlated negatively with several parameters of bone resorption. Conclusions In men with idiopathic osteoporosis, bone resorption is increased and exceeds bone formation. The excessive bone resorption seen in idiopathic male osteoporosis may be due to decreased estradiol levels and low levels of bioavailable testosterone. [source]


    Gender-specific differences in temporomandibular retrodiscal tissues of the goat

    EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 5 2000
    Angelo Mariotti
    Healthy, adult, male and female goat temporomandibular retrodiscal tissues were characterized to determine if biochemical differences existed between the genders. RNA concentrations were not different between male and female retrodiscal tissues; however, the DNA concentration in female retrodiscal tissues was 82% greater than in male retrodiscal tissues. Collagen concentrations were significantly greater in male retrodiscal tissues, and this was reflected in significant gender differences of type I and III collagen concentrations. More specifically, male temporomandibular retrodiscal tissues contained 70% more type I collagen and 119% more type III collagen when compared to female retrodiscal tissues. These differences in collagens and DNA reflect a gender difference in temporomandibular retrodiscal tissue composition that underlies divergent biomechanical and neurophysiological properties. [source]


    The role of exon 5 in fibroblast collagenase (MMP-1) substrate specificity and inhibitor selectivity

    FEBS JOURNAL, Issue 6 2001
    Vera Knäuper
    Interstitial collagen is degraded by members of the matrix metalloproteinase (MMP) family, including MMP-1. Previous work has shown that the region of MMP-1 coded for by exon 5 is implicated both in substrate specificity and inhibitor selectivity. We have constructed a chimeric enzyme, the exon 5 chimera, consisting primarily of MMP-1, with the region coded for by exon 5 replaced with the equivalent region of MMP-3, a noncollagenolytic MMP. Unlike MMP-3, the exon 5 chimera is capable of cleaving type I collagen, but the activity is only 2.2% of trypsin-activated MMP-1. ,Superactivation' of the chimera has no discernible effect, suggesting that the salt bridge formed in ,superactive' MMP-1 is not present. The kinetics for exon 5 chimera cleavage of two synthetic substrates display an MMP-3 phenotype, however, cleavage of gelatin is slightly impaired as compared to the parent enzymes. The Kiapp values for the exon 5 chimera complexed with synthetic inhibitors and N-terminal TIMP-2 also show a more MMP-3-like behaviour. However, the kon values for N-terminal TIMP-1 and N-terminal TIMP-2 are more comparable to those for MMP-1. These data show that the region of MMP-1 coded for by exon 5 is involved in both substrate specificity and inhibitor selectivity and the structural basis for our findings is discussed. [source]


    Urinary N-telopeptide levels in multiple myeloma patients, correlation with Tc-99m-sestaMIBI scintigraphy and other biochemical markers of disease activity

    HEMATOLOGICAL ONCOLOGY, Issue 1 2003
    M. G. Alexandrakis
    Abstract Urinary cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a sensitive and specific marker of bone resorption in multiple myeloma (MM). In this study, we measured the levels of NTx in 30 newly diagnosed MM patients and 25 controls. We examined its association with the overall score of skeletal involvement measured by Tc-99m-MIBI scintigraphy and other biochemical markers of bone disease (tumour necrosis factor a (TNF-a), serum calcium and creatinine). We further studied the correlation of NTx with the stage of disease (according to Durie,Salmon criteria) and bone marrow infiltration by plasma cells. High levels of NTx, bone marrow infiltration, TNF-,, calcium and creatinine were noted at advanced stages of disease (p,<,0.05). NTx and TNF-a were found at significantly higher concentrations in patients with a high overall score (3 and 4) in Tc-99m-sestaMIBI in comparison to a low score (0, 1 and 2; p,<,0.05). Positive correlations were found between NTx and TNF-a, as well as between bone infiltration and TNF-a or calcium. In conclusion, NTx is a useful marker for the monitoring of bone resorption in MM and correlates with imaging findings on Tc-99m-sestaMIBI and other biochemical markers of disease activity. Copyright © 2002 John Wiley & Sons, Ltd. [source]


    Foxf1 +/, mice exhibit defective stellate cell activation and abnormal liver regeneration following CCl4 injury

    HEPATOLOGY, Issue 1 2003
    Vladimir V. Kalinichenko
    Previous studies have shown that haploinsufficiency of the splanchnic and septum transversum mesoderm Forkhead Box (Fox) f1 transcriptional factor caused defects in lung and gallbladder development and that Foxf1 heterozygous (+/,) mice exhibited defective lung repair in response to injury. In this study, we show that Foxf1 is expressed in hepatic stellate cells in developing and adult liver, suggesting that a subset of stellate cells originates from septum transversum mesenchyme during mouse embryonic development. Because liver regeneration requires a transient differentiation of stellate cells into myofibroblasts, which secrete type I collagen into the extracellular matrix, we examined Foxf1 +/, liver repair following carbon tetrachloride injury, a known model for stellate cell activation. We found that regenerating Foxf1 +/, liver exhibited defective stellate cell activation following CCl4 liver injury, which was associated with diminished induction of type I collagen, ,,smooth muscle actin, and Notch-2 protein and resulted in severe hepatic apoptosis despite normal cellular proliferation rates. Furthermore, regenerating Foxf1 +/, livers exhibited decreased levels of interferon-inducible protein 10 (IP-10), delayed induction of monocyte chemoattractant protein 1 (MCP-1) levels, and aberrantly elevated expression of transforming growth factor ,1. In conclusion, Foxf1 +/, mice exhibited abnormal liver repair, diminished activation of hepatic stellate cells, and increased pericentral hepatic apoptosis following CCl4 injury. [source]


    Immunopathogenesis of hepatitis C virus infection and hepatic fibrosis: New insights into antifibrotic therapy in chronic hepatitis C

    HEPATOLOGY RESEARCH, Issue 8 2007
    Rosāngela Teixeira
    Fibrosis and cirrhosis represent the consequences of a sustained wound-healing response to chronic liver injury of any cause. Chronic hepatitis C virus (HCV) has emerged as a leading cause of cirrhosis in the USA and throughout the world. HCV may induce fibrogenesis directly by hepatic stellate cell activation or indirectly by promoting oxidative stress and apoptosis of infected cells. The ultimate result of chronic HCV injury is the accumulation of extracellular matrix with high density type I collagen within the subendothelial space of Disse, culminating in cirrhosis with hepatocellular dysfunction. The treatment of hepatitis C with the combination of pegylated interferon and ribavirin is still both problematic and costly, has suboptimal efficacy, serious side effects and a high level of intolerance, and is contraindicated in many patients. Hence, new approaches have assumed greater importance, for which there is an urgent need. The sustained progress in understanding the pathophysiology of hepatic fibrosis in the past two decades has increased the possibility of developing drugs specifically targeting the fibrogenic process. Future efforts should identify genetic markers associated with fibrosis risk in order to tailor the treatment of HCV infection based on genetically regulated pathways of injury and/or fibrosis. Such advances will expand the arsenal to overcome liver fibrosis, particularly in patients with hepatic diseases who have limited treatment options, such as those patients with chronic hepatitis C who have a high risk of fibrosis progression and recurrent HCV disease after liver transplantation. [source]


    Y-position cysteine substitution in type I collagen (,1(I) R888C/p.R1066C) is associated with osteogenesis imperfecta/Ehlers-Danlos syndrome phenotype,,

    HUMAN MUTATION, Issue 4 2007
    Wayne A. Cabral
    Abstract The most common mutations in type I collagen causing types II,IV osteogenesis imperfecta (OI) result in substitution for glycine in a Gly-Xaa-Yaa triplet by another amino acid. We delineated a Y-position substitution in a small pedigree with a combined OI/Ehlers-Danlos Syndrome (EDS) phenotype, characterized by moderately decreased DEXA z-score (,1.3 to ,2.6), long bone fractures, and large-joint hyperextensibility. Affected individuals have an ,1(I)R888C (p.R1066C) substitution in one COL1A1 allele. Polyacrylamide gel electrophoresis (PAGE) of [3H]-proline labeled steady-state collagen reveals slight overmodification of the ,1(I) monomer band, much less than expected for a substitution of a neighboring glycine residue, and a faint ,1(I) dimer. Dimers form in about 10% of proband type I collagen. Dimer formation is inefficient compared to a possible 25%, probably because the SH-side chains have less proximity in this Y-position than when substituting for a glycine. Theoretical stability calculations, differential scanning calorimetry (DSC) thermograms, and thermal denaturation curves showed only weak local destabilization from the Y-position substitution in one or two chains of a collagen helix, but greater destabilization is seen in collagen containing dimers. Y-position collagen dimers cause kinking of the helix, resulting in a register shift that is propagated the full length of the helix and causes resistance to procollagen processing by N-proteinase. Collagen containing the Y-position substitution is incorporated into matrix deposited in culture, including immaturely and maturely cross-linked fractions. In vivo, proband dermal fibrils have decreased density and increased diameter compared to controls, with occasional aggregate formation. This report on Y-position substitutions in type I collagen extends the range of phenotypes caused by nonglycine substitutions and shows that, similar to X- and Y-position substitutions in types II and III collagen, the phenotypes resulting from nonglycine substitutions in type I collagen are distinct from those caused by glycine substitutions. Hum Mutat 28(4), 396,405, 2007. Published 2007 Wiley-Liss, Inc. [source]


    Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans,,

    HUMAN MUTATION, Issue 3 2007
    Joan C. Marini
    Abstract Osteogenesis imperfecta (OI) is a generalized disorder of connective tissue characterized by fragile bones and easy susceptibility to fracture. Most cases of OI are caused by mutations in type I collagen. We have identified and assembled structural mutations in type I collagen genes (COL1A1 and COL1A2, encoding the pro,1(I) and pro,2(I) chains, respectively) that result in OI. Quantitative defects causing type I OI were not included. Of these 832 independent mutations, 682 result in substitution for glycine residues in the triple helical domain of the encoded protein and 150 alter splice sites. Distinct genotype,phenotype relationships emerge for each chain. One-third of the mutations that result in glycine substitutions in ,1(I) are lethal, especially when the substituting residues are charged or have a branched side chain. Substitutions in the first 200 residues are nonlethal and have variable outcome thereafter, unrelated to folding or helix stability domains. Two exclusively lethal regions (helix positions 691,823 and 910,964) align with major ligand binding regions (MLBRs), suggesting crucial interactions of collagen monomers or fibrils with integrins, matrix metalloproteinases (MMPs), fibronectin, and cartilage oligomeric matrix protein (COMP). Mutations in COL1A2 are predominantly nonlethal (80%). Lethal substitutions are located in eight regularly spaced clusters along the chain, supporting a regional model. The lethal regions align with proteoglycan binding sites along the fibril, suggesting a role in fibril,matrix interactions. Recurrences at the same site in ,2(I) are generally concordant for outcome, unlike ,1(I). Splice site mutations comprise 20% of helical mutations identified in OI patients, and may lead to exon skipping, intron inclusion, or the activation of cryptic splice sites. Splice site mutations in COL1A1 are rarely lethal; they often lead to frameshifts and the mild type I phenotype. In ,2(I), lethal exon skipping events are located in the carboxyl half of the chain. Our data on genotype,phenotype relationships indicate that the two collagen chains play very different roles in matrix integrity and that phenotype depends on intracellular and extracellular events. Hum Mutat 28(3), 209,221, 2007. Published 2006 Wiley-Liss, Inc. [source]


    Ultrastructural and immunocytochemical characterization of immortalized odontoblast MO6-G3

    INTERNATIONAL ENDODONTIC JOURNAL, Issue 6 2006
    C. Mesgouez
    Abstract Aim, To investigate an immortalized murine odontoblast cell line as a potential alternative for experimental studies on dentinogenesis. Methodology, The MO6-G3 cell line was investigated morphologically over 3, 7, 11 and 42 days of culture, using histochemical localization of dentine sialoprotein (DSP), alkaline phosphatase (AP), type I collagen and actin filaments, histoenzymatic staining and biochemical investigation of AP and finally, transmission and scanning electron microscopy. Results, Scanning electron micrographs showed elongated cells. Accordingly, a polarized organization of odontoblasts was observed by transmission electron microscopy, identifying distinct subcellular compartments as described in vivo. The secretion apparatus, which includes cisternae of rough endoplasmic reticulum, Golgi apparatus saccules and secretion vesicles and granules, was longitudinally organized in the supranuclear compartment ending distally in the secretory pole. A cellular process was observed. The investigation of the cytoskeleton network revealed that actin microfilaments were organized in parallel stress fibre oriented depending on the longitudinal axis of the cytoplasm. Immunofluorescent labelling showed a continuous expression of type I collagen, DSP and AP. A unipolar distribution characterized intracellular DSP immunoreactivity. Histoenzymology revealed AP active sites increasing from 3 to 11 days albeit with a moderate level of activity comparatively to the in vivo situation in dental cells. Conclusion, This cell line MO6-G3 not only showed the criteria of odontoblast phenotype as previously reported but also the characteristic morphodifferentiation pattern of polarized odontoblasts at the cellular level but with an apparent random distribution. [source]


    Immunolocalization of bone extracellular matrix proteins (type I collagen, osteonectin and bone sialoprotein) in human dental pulp and cultured pulp cells

    INTERNATIONAL ENDODONTIC JOURNAL, Issue 6 2003
    J. M. Q. Garcia
    Abstract Aim, To simultaneously analyse the expression of type I collagen, osteonectin and bone sialoprotein (BSP) in human dental pulp of different ages. Methodology, Cultured dental pulp fibroblasts (FP1 cell line), pulps from dental germs with incomplete root formation (n = 4) and pulps of erupted teeth with total root formation (n = 4) were used. Bone proteins were searched by immunohistochemistry and immunofluorescence using polyclonal antibodies and compared among the three groups assessed. Results, Immunohistochemistry detected the three proteins in dental pulp tissue, as it labelled extracellular matrix, predentine and odontoblasts. The BSP label was weaker, when compared to both type I collagen and osteonectin. The presence of type I collagen was more evident in pulps from erupted teeth, when compared to germ dental pulps. On the other hand, a strong expression of osteonectin in germ dental pulps was observed. Conclusions, Regardless of the degree of maturation, dental pulps present type I collagen, osteonectin and BSP in the extracellular matrix (ECM) and in the odontoblastic layer. Thus, the results suggest that these proteins are related to the production and mineralization of dentine. [source]


    Bone turnover 18 months after a single intravenous dose of zoledronic acid

    INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 6 2007
    V. Z. C. Borba
    Summary Zoledronic acid inhibits bone resorption for up to 12 months. It is not known whether the duration of this antiresorptive effect extends beyond this period of time. The aim of this study was to evaluate the changes in bone turnover at 12 months (T12) and 18 months (T18) after a single injection of 4 mg of zoledronic acid. It is a prospective, longitudinal study, with a follow-up for 18 months. We studied male and female patients (60.5 ± 11.0 years old), with low bone mineral density (BMD) coming from the outpatient clinic in a metabolic bone unit of a tertiary care hospital. All patients received a single intravenous dose of 4 mg of zoledronic acid, bone turnover markers [serum carboxyterminal telopeptide of type I collagen (CTX-I), bone-specific alkaline phosphatase (BSAP)] and BMD [lumbar spine (LS) and total hip (TH)] were measured at baseline, and after 12 months (T12) and 18 months (T18). Median serum CTX-I and BSAP levels were suppressed at T12 in comparison with baseline values: 0.183 to 0.039 ng/ml for CTX-I (p = 0.0002) and 16.95 to 13.96 U/l for BSAP (p = 0.005). At T18, both CTX-I and BSAP continued to be suppressed below baseline at 0.108 ng/ml and 12.23 U/l (p = 0.009 and p = 0.02, vs. T0). Significant increases in BMD at T18 as compared with T12 were observed in patients (median increase 6.1% for LS and 2.0% for TH). Zoledronic acid inhibits bone turnover effectively for 12 months, with evidence for continued suppression and gains in BMD even after 18 months. [source]


    Chronic acid ingestion promotes renal stone formation in rats treated with vitamin D3

    INTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2007
    Naohiko Okamoto
    Objective: Although hypercalciuria, a well-established adverse effect of vitamin D3, can be a risk factor of renal stone formation, the risk of nephrolithiasis has not been well defined. The consumption of a diet high in acid precursors is often cited as a risk factor for the development of calcium-based kidney stones. In the present study, we investigated the effect of chronic acid ingestion on kidney stone formation in rats treated with calcitriol (1,25[OH]2 D3). Methods: Control rats (C-C), calcitriol-treated rats (C-V; three treatments of 0.5 µg of calcitriol per week) and acid-ingested (water containing 0.21 mol/L NH4Cl), calcitriol-treated (three treatments of 0.5 µg of calcitriol per week) rats (A-V) were fed in metabolic cages. After 1 month, urine, blood, kidney and bone samples were analyzed. Results: The A-V rats exhibited elevated serum calcium concentrations, urinary calcium and phosphate excretion, urinary type I collagen cross-linked N-peptide (NTx)/creatinine values, mRNA expression of osteopontin in the kidney, and renal calcium contents as well as decreased bone mineral densities, compared with the C-C and C-V rats. Urinary citrate excretion was lower and NaDC-1 mRNA expression in the kidney was higher in the A-V rats than in the C-C and C-V rats. Calcium phosphate kidney stones were found in the A-V rats. Conclusions: The ingestion of NH4Cl, an acid precursor, promotes calcium phosphate kidney stone formation in calcitriol-treated rats. The chronic intake of a diet rich in acid precursors may be a risk factor for the development of kidney stones in subjects who are being treated with calcitriol. [source]


    Heterogeneity in Serum 25-Hydroxy-Vitamin D Response to Cholecalciferol in Elderly Women with Secondary Hyperparathyroidism and Vitamin D Deficiency

    JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2010
    Andrea Giusti MD
    OBJECTIVES: To compare the effects on parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25(OH)D) of two dosing regimens of cholecalciferol in women with secondary hyperparathyroidism (sHPTH) and hypovitaminosis D and to investigate variables affecting 25(OH)D response to cholecalciferol. DESIGN: Randomized-controlled trial with 6-month follow-up. SETTING: Two osteoporosis centers in northern Italy. PARTICIPANTS: Sixty community-dwelling women aged 65 and older with sHPTH and hypovitaminosis D, creatinine clearance greater than 65 mL/min and without diseases or drugs known to influence bone and vitamin D metabolism. INTERVENTION: Cholecalciferol 300,000 IU every 3 months, once at baseline and once at 3 months (intermittent D3 group) or cholecalciferol 1,000 IU/day (daily D3 group). MEASUREMENTS: Serum PTH, 25(OH)D, calcium, bone-specific alkaline phosphatase, ,-C-terminal telopeptide of type I collagen, phosphate, 24-hour urinary calcium excretion. RESULTS: The two groups had similar baseline characteristics. All participants had vitamin D deficiency [25(OH)D<20 ng/mL)], and 36 subjects (60%) had severe deficiency (<10 ng/mL), with no difference between the groups (severe deficiency: intermittent D3 group, n=18; daily D3 group, n=18). After 3 and 6 months, both groups had a significant increase in 25(OH)D and a reduction in PTH. Mean absolute increase±standard deviation of 25(OH)D at 6 months was higher in the intermittent D3 group (22.7±11.8 ng/mL) than in the daily D3 group (13.7±6.7 ng/mL, P<.001), with a higher proportion of participants in the intermittent D3 group reaching desirable serum concentration of 25(OH)D , 30 ng/mL (55% in the intermittent D3 group vs 20% in the daily D3 group, P<.001). Mean percentage decrease of PTH in the two groups was comparable, and at 6 months, a similar proportion of participants reached normal PTH values. 25(OH)D response to cholecalciferol showed a wide variability. In a logistic regression analysis, body mass index and type of treatment appeared to be significantly associated with normalization of 25(OH)D values. CONCLUSION: Cholecalciferol 300,000 IU every 3 months was more effective than 1,000 IU daily in correcting vitamin D deficiency, although the two groups achieved similar effects on PTH at 6 months. Only 55% of the higher-dose intermittent group reached desirable concentrations of 25(OH)D, suggesting that yet-higher doses will be required for adequate vitamin D repletion. [source]


    The hip joint: the fibrillar collagens associated with development and ageing in the rabbit

    JOURNAL OF ANATOMY, Issue 1 2001
    YVETTE S. BLAND
    The fibrillar collagens associated with the articular cartilages, joint capsule and ligamentum teres of the rabbit hip joint were characterised from the 17 d fetus to the 2-y-old adult by immunohistochemical methods. Initially the putative articular cartilage contains types I, III and V collagens, but when cavitation is complete in the 25 d fetus, type II collagen appears. In the 17 d fetus, the cells of the chondrogenous layers express type I collagen mRNA, but not that of type II collagen. Types III and V collagens are present throughout life, particularly pericellularly. Type I collagen is lost. In all respects, the articular cartilage of the hip joint is similar to that of the knee. The joint capsule contains types I, III and V collagens. In the fetus the ligamentum teres contains types I and V collagens and the cells express type I collagen mRNA; type III collagen is confined mainly to its surface and insertions. After birth, the same distribution remains, but there is more type III collagen in the ligament, proper. The attachment to the cartilage of the head of the femur is marked only by fibres of type I collagen traversing the cartilage; the attachment cannot be distinguished in preparations localising types III and V collagens. The attachment to the bone at the lip of the acetabulum is via fibres of types I and V collagens and little type III is present. The ligament is covered by a sheath of types III and V collagens. Type II collagen was not located in any part of the ligamentum teres. The distribution of collagens in the ligamentum teres is similar to that in the collateral ligaments of the knee. Its insertions are unusual because no fibrocartilage was detected. [source]


    Preparation and characterization of complex gel of type I collagen and aluminosilicate containing imogolite nanofibers

    JOURNAL OF APPLIED POLYMER SCIENCE, Issue 4 2010
    Asuka Nakano
    Abstract Complex gel materials of Type I collagen and aluminosilicate containing imogolite nanofibers were prepared as opaque gel by mixing an acidic fine dispersion of aluminosilicate with an acidic solution of collagen. The product was stained blue by Coomassie Brilliant Blue (CBB), indicating that the gel contained collagen. A white sponge was obtained after lyophilization of the complex gel. Elemental analysis revealed that the complex contains C, H, N, Al, and Si atoms; and the compositional ratio of aluminosilicate/collagen (w/w) was calculated as 0.75 for the complex gel when aluminosilicate was mixed with an equal quantity of collagen. Transmission electron microscope (TEM) observation showed that aluminosilicate nanofibers were homogeneously distributed in the collagen matrix. The thermogravimetric analysis (TGA) curve of the complex was not a simple summation of each components, and especially, the weight loss step corresponding to detachment of the adsorbed water observed in aluminosilicate became difficult to distinguish, suggesting that the adsorbed water was removed in the complexation. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 [source]


    Novel thermostable serine collagenase from Thermoactinomyces sp.

    JOURNAL OF BASIC MICROBIOLOGY, Issue 4 2006
    21E: purification, some properties
    A thermophilic actinomycete strain Thermoactinomyces sp. 21E producing a highly thermostable serine collagenase was isolated from Bulgarian soil. The collagenase, produced extracellular by Thermoactinomyces sp. 21E, was purified to homogeneity by heat treatment, ultrafiltration, saturation with ammonium sulfate and gel filtration chromatography with a 101-fold increase in specific activity and 58% recovery. The collagenase has a relative molecular mass of 50000 by SDS-PAGE. The optimum temperature for the enzyme activity was 60,65 °C in the absence of Ca2+ and 70,75 °C in the presence of Ca2+. About 40% of the original activity remaining after incubation at 85 °C for 30 min in the presence of Ca2+. The optimum pH for the enzyme activity was 9.0,9.5 and the enzyme was stable for 1h at 70 °C in the pH range from 7.5 to 12.5. The collagenase was strongly inhibited by active-site inhibitors of serine protease PMSF and DFP, which indicated that the enzyme is serine protease. The enzyme activity was completely inhibited by Hg2+, Cu2+ and Fe2+. However, Ca2+ strongly activated the collagenase activity. The collagenase from Thermoactinomyces sp. 21E showed high activity toward type I collagen, acid-soluble collagen, gelatin and Pz-PLGPR. However, elastin for collagenase was inert as substrate. The properties of the collagenase from strain 21E suggest that this enzyme is a new collagenolytic protease that differs from the collagenases and serine proteases reported so far. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]


    Natural bone collagen scaffold combined with OP-1 for bone formation induction in vivo

    JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2009
    Yu Qian
    Abstract The scaffold is a key element to osteogenic tissue engineering as it provides a microenvironment for bone formation. Natural bone collagen scaffold (NBCS) is a novel biomaterial scaffold acid-extracted from organic human bone. The objective of this study was to characterize NBCS and evaluate the osteoconductivity of the scaffold, in combination with osteogenic protein-1 (OP-1), using a rabbit posteolateral lumbar fusion model. Thirty two rabbits were divided into 4 experimental groups, autograft, NBCS alone, OP-1 alone or NBCS combined with OP-1. Bone formation was evaluated by micro-CT, quantitative histological analysis, immunohistochemistry and semi-quantitative RT-PCR at 6 weeks postoperatively. By scanning electronic microscope, we showed that NBCS maintains a porous, interconnecting microarchitecture. Micro-CT analysis demonstrated that NBCS combined with OP-1 significantly induced (p < 0.01) bone formation at the fusion site as compared to control groups. This was confirmed by quantitative histological analysis which demonstrated that the NBCS combined with OP-1 significantly enhanced bone matrix area (17.7 mm2) (p < 0.05) and bone marrow cavity size (71.3 mm2) (p < 0.05) as compared to the controls. Immunohistochemical assessment and RT-PCR also demonstrated that NBCS combined with OP-1 enhanced type I collagen and osteonectin expression. Together, these results suggest that NBCS is an effective scaffold for osteogenesis, and combined with growth factors such as OP-1, possesses both osteoconductive and osteoinductive properties that are sufficient for bone regeneration. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009 [source]


    Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2010
    Delnaz Roshandel
    Abstract The aim of this study was to determine if single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r2,,,0.8) were selected for RANKL, RANK, and OPG and their 10-kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome-wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population-based study of male aging, the European Male Ageing Study (EMAS). N-terminal propeptide of type I procollagen (PINP) and C-terminal cross-linked telopeptide of type I collagen (CTX-I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total-hip areal BMD (BMDa) was measured by dual-energy X-ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP (,,=,1.83, p,=,.004) and CTX-I (,,=,17.59, p,=,4.74,×,10,4), and lower lumbar spine BMDa (,,=,,0.02, p,=,.026). The minor allele of rs9594759 (C) was associated with lower PINP (,,=,,1.84, p,=,.003) and CTX-I (,,=,,27.02, p,=,6.06,×,10,8) and higher ultrasound BMD at the calcaneus (,,=,0.01, p,=,.037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men. © 2010 American Society for Bone and Mineral Research [source]