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Joint Cavity (joint + cavity)
Selected AbstractsDifferential regulation of GDF-5 and FGF-2/4 by immobilisation in ovo exposes distinct roles in joint formation,DEVELOPMENTAL DYNAMICS, Issue 3 2006E. Kavanagh Abstract Members of the fibroblast growth factor (FGF) family and growth and differentiation factor 5 (GDF-5) have been implicated in joint specification, but their roles in subsequent cavity formation are not defined. Cavity formation (cavitation) depends upon limb movement in embryonic chicks and factors involved in joint formation are often identified by their expression at the joint-line. We have sought support for the roles of FGF-2, FGF-4, and GDF-5 in cavitation by defining expression patterns, immunohistochemically, during joint formation and establishing whether these are modified by in ovo immobilisation. We found that FGF-2 exhibited low level nuclear expression in chondrocytes and fibrocartilage cells close to presumptive joints, but showed significantly higher expression levels in cells at, and directly bordering, the forming joint cavity. This high-level joint line FGF-2 expression was selectively diminished in immobilised limbs. In contrast, we show that FGF-4 does not exhibit differential joint-line expression and was unaffected by immobilisation. GDF-5 protein also failed to show joint-line selective labelling, and although immobilisation induced a cartilaginous fusion across presumptive joints, it did not affect cellular GDF-5 expression patterns. Examining changes in GDF-5 expression in response to a direct mechanical strain stimulus in primary embryonic chick articular surface (AS) cells in vitro discloses only small mechanically-induced reductions in GDF-5 expression, suggesting that GDF-5 does not exert a direct positive contribution to the mechano-dependent joint cavitation process. This notion was supported by retroviral overexpression of UDPGD, a characteristic factor involved in hyaluronan (HA) accumulation at presumptive joint lines, which was also found to produce small decreases in AS cell GDF-5 expression. These findings support a direct mechano-dependent role for FGF-2, but not FGF-4, in the cavitation process and indicate that GDF-5 is likely to influence chondrogenesis positively without contributing directly to joint cavity formation. Developmental Dynamics 235:826,834, 2006. © 2006 Wiley-Liss, Inc. [source] Defining boundaries during joint cavity formation: going out on a limbINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2003K. J. Lamb Summary., Whilst factors controlling the site at which joints form within the developing limb are recognised, the mechanisms by which articular element separation occurs during the formation of the joint cavity have not been determined. Herein, we review the relationships between early limb patterning, embryonic movement, extracellular matrix composition, local signalling events and the process of joint cavity formation. We speculate that a pivotal event in this process involves the demarcation of signalling boundaries, established by local mechano-dependent modifications in glycosaminoglycan synthesis. In our opinion, studies that examine early patterning and also focus on local developmental alterations in tissue architecture are required in order to help elucidate the fundamental principals regulating joint formation. [source] PRG4 exchange between the articular cartilage surface and synovial fluidJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 10 2007G.E. Nugent-Derfus Abstract The boundary lubrication function of articular cartilage is mediated in part by proteoglycan 4 (PRG4) molecules, found both in synovial fluid (SF) and bound to the articular cartilage surface. Currently the mechanism by which PRG4 binds to the articular surface is not well understood. The objectives of this study were to determine (1) the effect of bathing fluid contents on PRG4 concentration at the articular surface ([PRG4]cart), and (2) whether native PRG4 can be removed from the surface and subsequently repleted with PRG4 from synovial fluid. In one experiment, cylindrical cartilage disks were stored in solutions of various PRG4 concentrations, either in phosphate-buffered saline (PBS) or SF as the carrier fluid. In a separate experiment, cartilage disks were stored in solutions expected to remove native PRG4 from the articular surface and allow subsequent repletion with PRG4 from SF. [PRG4]cart was independent of PRG4 concentration of the bathing fluid, and was similar for both carrier fluids. PRG4 was removed from cartilage by treatment with hyaluronidase, reduction/alkylation, and sodium dodecyl sulphate, and was repleted fully by subsequent bathing in SF. These results suggest that the articular surface is normally saturated with tightly bound PRG4, but this PRG4 can exchange with the PRG4 in SF under certain conditions. This finding suggests that all tissues surrounding the joint cavity that secrete PRG4 into the SF may help to maintain lubrication function at the articular surface. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1269,1276, 2007 [source] Efficacy of chitosan microspheres for controlled intra-articular delivery of celecoxib in inflamed jointsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2004Hetal Thakkar The use of polymeric carriers in formulations of therapeutic drug delivery systems has gained widespread application, due to their advantage of being biodegradable and biocompatible. In this study, we aimed to prepare celecoxib-loaded chitosan microspheres for intra-articular administration and to compare the retention of the celecoxib solution and chitosan microspheres in the joint cavity. The microspheres were characterized for entrapment efficiency, particle size and surface morphology by scanning electron microscopy. In-vitro drug release studies of microspheres revealed that the microspheres are able to control the release of celecoxib over a period of 96 h. Biodistribution studies of celecoxib and chitosan microspheres were performed by radiolabelling with 99mTc and injecting intra-articularly in rats. The study indicated that following intra-articular administration the distribution of the drug to the organs, like liver and spleen, is very rapid compared with that of the microspheres. Compared with the drug solution, a 10-fold increase in the concentration of the drug in the joint was observed 24 h post intra-articular injection (P < 0.005) when drug was encapsulated in microspheres. [source] Osteosarcoma near joints: Assessment and implicationsJOURNAL OF SURGICAL ONCOLOGY, Issue 3 2005Gerald M.Y. Quan MBBS Abstract Background The choice of performing surgery when tumors encroach onto joints remains a challenging and controversial issue. Pre-operative assessment by magnetic resonance imaging (MRI) is of critical importance in dictating surgical management and subsequent functional outcome. Methods We examined archival samples from 27 patients with osteosarcoma, adjacent to synovial joints for the incidence and mechanism of osteosarcoma extension into the joint space. Histopathologic findings were correlated with pre-operative MRI findings and choice of operation. Results There was no evidence of penetration across the entire thickness of articular cartilage into the joint cavity in all of the 27 cases. When pre-operative MRI confidently excluded joint involvement by tumor, enabling an intra-articular surgical approach, histopathologic correlation confirmed the absence of joint involvement in all cases. The low incidence of joint involvement was despite the presence of extensive bone and soft tissue involvement in most cases, a tendency for peripheral extension of tumor around the articular margin of the bone, and evidence of joint effusions pre-operatively in more than one-third of cases. Conclusions Joint involvement by osteosarcoma is uncommon, with articular cartilage being a relative barrier to tumor invasion. If pre-operative MRI does not show definite evidence of intra-articular tumor involvement, it is likely to be safe to proceed with intra-articular resection. J. Surg. Oncol. 2005;91:159,166. © 2005 Wiley-Liss, Inc. [source] Effects of Arg-Gly-Asp Sequence Peptide and Hyperosmolarity on the Permeability of Interstitial Matrix and Fenestrated Endothelium in JointsMICROCIRCULATION, Issue 6 2004A. POLI ABSTRACT Objectives: The aims were to assess the contribution of arg-gly-asp (RGD) mediated cell integrin,matrix bonds to interstitial hydraulic resistance and to fenestrated endothelial permeability in joints. Joint fluid is generated by filtration from fenestrated capillaries and drains through a fibronectin-rich synovial intercellular matrix. The role of parenchymal cell,matrix bonding in determining tissue hydraulic resistance is unknown. Methods: The knee cavity of anesthetized rabbits was infused with saline or the competitive hexapeptide blocker GRGDTP, with or without added osmotic stress (600 mosm saline). Intra-articular pressure Pj, net trans-synovial drainage rate s, and the permeation of Evans blue-labeled albumin (EVA) from plasma into the joint cavity were measured. Results: GRGDTP increased the hydraulic conductance of the synovial drainage pathway, ds/dPj, by 71% (p = .02, paired t test, n = 6 animals). Synovial plasma EVA clearance (control 7.1 ± 0.8 ,L h,1, mean ± SEM, n = 15) was unaffected by GRGDTP (7.0 ± 2.3 ,L h,1, n = 6) or hyperosmolarity (4.9 ± 1.5 ,L h,1, n = 8) but was increased by GRGDTP and hyperosmolarity together (15.9 ± 4.8 ,L h,1, n = 5) (p = .01, ANOVA). Changes in dPj/dt evoked by GRGDTP plus hyperosmolarity, but neither alone, demonstrated increased microvascular filtration into the joint cavity (p < .001, ANOVA), as did changes in fluid absorption from the infusion system at fixed Pj. Conclusions: RGD-mediated bonds between the parenchymal cells and interstitial polymers reduce the interstitial hydraulic conductance by 42%. This helps to retain the lubricating fluid inside a joint cavity. RGD-mediated bonds also support the macromolecular barrier function of fenestrated endothelium, but in vivo this is evident only in stressed endothelium (cf. in vitro). [source] Signal pathways regulating hyaluronan secretion into static and cycled synovial joints of rabbitsTHE JOURNAL OF PHYSIOLOGY, Issue 17 2009K. R. Ingram Joint lubrication, synovial fluid conservation and many pathophysiological processes depend on hyaluronan (HA). Intra-articular HA injection and exercise, which stimulates articular HA production, ameliorate osteoarthritis. We therefore investigated the pathways regulating movement-stimulated articular HA secretion rate () in vivo. Endogenous HA was removed from the knee joint cavity of anaesthetised rabbits by washout. Joints were then cycled passively or remained static for 5 h, with/without intra-articular agonist/inhibitor, after which newly secreted HA was harvested for analysis. Movement almost doubled . Similar or larger increases were elicited in static joints by the intra-articular Ca2+ ionophore ionomycin, prostaglandin E2, cAMP-raising agents, serine/threonine phosphatase inhibitor and activation of protein kinase C (PKC). PKC-stimulated secretion was inhibited by the PKC inhibitor bisindolylmaleimide I and inhibitors of the downstream kinases MEK-ERK (U0126, PD98059). These agents inhibited movement-stimulated secretion of HA (MSHA) only when the parallel p38 kinase path was simultaneously inhibited by SB203580 (ineffective alone). The phospholipase C inhibitor U73122 almost fully blocked MSHA (P= 0.001, n= 10), without affecting static . The ENaC channel blocker amiloride inhibited MSHA, whereas other inhibitors of stretch-activated channels (Gd3+, ruthenium red, SKF96365) did not. It is proposed that MSHA may be mediated by PLC activation, leading to activation of parallel PKC,MEK,ERK and p38 kinase pathways. [source] Protective effects of plasmin(ogen) in a mouse model of Staphylococcus aureus,induced arthritisARTHRITIS & RHEUMATISM, Issue 3 2008Yongzhi Guo Objective To assess the functional roles of plasmin in a murine model of Staphylococcus aureus,induced bacterial arthritis. Methods Bacterial arthritis was induced in plasminogen-deficient (Plg,/,) and wild-type (Plg+/+) littermates by local injection of 1 × 106 colony-forming units of S aureus into the knee joints. Human plasminogen was administered to Plg,/, mice on days 0,7 or days 7,14. Antibiotic treatment was administered to Plg,/, mice on days 7,14. Bacteria counts and histologic, immunohistochemical, and Western blot analyses were performed. Results In Plg+/+ mice, S aureus counts had declined within 2 days, and by day 28 the bacteria had been completely eliminated. However, S aureus was still detectable in all injected joints from Plg,/, mice, and bacteria counts were 27 times higher than the amount injected on day 0. The extent of macrophage and neutrophil recruitment to the infected joints was comparable for Plg+/+ and Plg,/, mice on days 1, 7, and 14. The activation of these inflammatory cells appeared to be impaired in Plg,/, mice, however. Treatment of Plg,/, mice with antibiotic (cloxacillin) resulted in successful killing of the bacteria, but the necrotic tissue remained in the infected joints. When human plasminogen was given intravenously to Plg,/, mice daily for 7 days, bacterial clearance was greatly improved as compared with their untreated counterparts, and the amount of necrotic tissue in the joint cavity was dramatically reduced. The expression of interleukin 6 (IL-6) and IL-10 was higher in Plg+/+ mice than in Plg,/, mice during bacterial arthritis. Conclusion Our findings indicate that plasmin plays a pluripotent role in protecting against S aureus,induced arthritis by activating inflammatory cells, killing bacteria, removing necrotic tissue, and enhancing cytokine expression. [source] | |||||||||||||