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Joint Degeneration (joint + degeneration)
Selected AbstractsJoint degeneration following closed intraarticular fracture in the mouse knee: A model of posttraumatic arthritisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2007Bridgette D. Furman Abstract Posttraumatic arthritis is one of the most frequent causes of disability following joint trauma. The objective of this study was to develop a model of a closed articular fracture in the mouse knee joint to quantify the temporal sequence of joint degeneration in a model of posttraumatic arthritis. Closed intraarticular fractures were created in the tibial plateau of adult mice (C57BL/6) using a computer-controlled materials testing system and a custom-built indenter tip. Tibial plateau fractures were classified and imaged over time using high-resolution digital radiography. Animals were sacrificed at 2, 4, 8, and 50 weeks following fracture, and the experimental and contralateral control limbs were harvested for histology and micro-computed tomography (microCT) analysis. By radiographic analysis, tibial plateau fractures closely resembled clinical fractures. More complex and comminuted fractures correlated to significantly higher fracture energies. Histologic analysis demonstrated progressive joint degeneration as measured by a modified Mankin scale, with fibrillation and loss of proteoglycan in the articular cartilage. Subchondral bone thickening was also observed in experimental joints. The induction of a closed intraarticular fracture of the mouse tibial plateau generated a reproducible and clinically relevant joint injury that progressed to osteoarthritis-like changes by histologic and microCT evaluations. The ability to induce joint degeneration without an osteotomy or open arthrotomy provides a valuable new model for studying the natural sequelae of posttraumatic arthritis. Notably, the use of a murine model will facilitate the use of genetically modified animals for the investigation of specific genes implicated in the pathology of posttraumatic arthritis. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:578,592, 2007 [source] Current approaches in haemophilic arthropathy of the hipHAEMOPHILIA, Issue 3 2009H. A. MANN Summary., The hip is considered to be one of the main load bearing joints of the body. In the haemophilic patient joint bleeds can be catastrophic, leading to long-term joint degeneration and accompanying arthritis. In this review we explore the mechanisms of joint destruction, with particular consideration of the anatomy of the hip and how it may influence disease progression. We also review current strategies for treatment including hip replacement in the haemophilic patient and describe our experiences as a unit. Finally we evaluate future prospects in the management of hip disease in haemophilia. [source] The Colorado Haemophilia Paediatric Joint Physical Examination Scale: normal values and interrater reliabilityHAEMOPHILIA, Issue 1 2007M. R. HACKER Summary., ,Persons with haemophilia often experience their first joint haemorrhage in early childhood. Recurrent bleeding into a joint may lead to significant morbidity, specifically haemophilic arthropathy. Early identification of the onset and progression of joint damage is critical to preserving joint structure and function. Physical examination is the most feasible approach to monitor joint health. Our group developed the Colorado Haemophilia Paediatric Joint Physical Examination Scale to identify earlier signs of joint degeneration and incorporate developmentally appropriate tasks for assessing joint function in young children. This study's objectives were to establish normal ranges for this scale and assess interrater reliability. The ankles, knees and elbows of 72 healthy boys aged 1 through 7 years were evaluated by a physical therapist to establish normal ranges. Exactly 10 boys in each age category from 2 to 7 years were evaluated by a second physical therapist to determine interrater reliability. The original scale was modified to account for the finding that mild angulation in the weight-bearing joints is developmentally normal. The interrater reliability of the scale ranged from fair to good, underscoring the need for physical therapists to have specific training in the orthopaedic assessment of very young children and the measurement error inherent in the goniometer. Modifications to axial alignment scoring will allow the scale to distinguish healthy joints from those suffering frequent haemarthroses. [source] Joint degeneration following closed intraarticular fracture in the mouse knee: A model of posttraumatic arthritisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2007Bridgette D. Furman Abstract Posttraumatic arthritis is one of the most frequent causes of disability following joint trauma. The objective of this study was to develop a model of a closed articular fracture in the mouse knee joint to quantify the temporal sequence of joint degeneration in a model of posttraumatic arthritis. Closed intraarticular fractures were created in the tibial plateau of adult mice (C57BL/6) using a computer-controlled materials testing system and a custom-built indenter tip. Tibial plateau fractures were classified and imaged over time using high-resolution digital radiography. Animals were sacrificed at 2, 4, 8, and 50 weeks following fracture, and the experimental and contralateral control limbs were harvested for histology and micro-computed tomography (microCT) analysis. By radiographic analysis, tibial plateau fractures closely resembled clinical fractures. More complex and comminuted fractures correlated to significantly higher fracture energies. Histologic analysis demonstrated progressive joint degeneration as measured by a modified Mankin scale, with fibrillation and loss of proteoglycan in the articular cartilage. Subchondral bone thickening was also observed in experimental joints. The induction of a closed intraarticular fracture of the mouse tibial plateau generated a reproducible and clinically relevant joint injury that progressed to osteoarthritis-like changes by histologic and microCT evaluations. The ability to induce joint degeneration without an osteotomy or open arthrotomy provides a valuable new model for studying the natural sequelae of posttraumatic arthritis. Notably, the use of a murine model will facilitate the use of genetically modified animals for the investigation of specific genes implicated in the pathology of posttraumatic arthritis. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:578,592, 2007 [source] Proposed model of botulinum toxin-induced muscle weakness in the rabbitJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2005D. Longino Abstract Osteoarthritic patients show only a weak association between radiographic signs of joint disease and joint pain and disability. Conversely, muscle weakness is one of the earliest and most common symptoms of patients with osteoarthritis (OA). However, while many experimental models of osteoarthritis include a component of muscular weakness, no model has isolated this factor satisfactorily. Therefore, the purpose of this study was to develop and validate an experimental animal model of muscle weakness for future use in the study of OA. Botulinum Type-A toxin (BTX-A) was uni-laterally injected into the quadriceps musculature of New Zealand white rabbits (3.5 unit/kg). Isometric knee extensor torque at a range of knee angles and stimulation frequencies, and quadriceps muscle mass, were quantified for control animals, and at one- and six-months post-repeated injections, in both, the experimental and the contralateral hindlimb. Ground reaction forces were measured in all animals while hopping across two force platforms. Isometric knee extension torque and quadriceps muscle mass was systematically decreased in the experimental hindlimb. Vertical ground reaction forces in the push off phase of hopping were also decreased in the experimental compared to control hindlimbs. We conclude that BTX-A injection into the rabbit musculature creates functional and absolute muscle weakness in a reproducible manner. Therefore, this model may be used to systematically study the possible effects of muscle weakness on joint degeneration, either as an isolated intervention, or in combination with other interventions (anterior cruciate ligament transection, meniscectomy) known to create knee joint degeneration. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Kinematics of the ACL-deficient canine knee during gait: Serial changes over two yearsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2004Scott Tashman Abstract The ACL-deficient dog is a model for investigating the development and progression of mechanically driven osteoarthrosis of the knee. ACL loss creates dynamic instability in the ACL-deficient knee which presumably leads to progressive joint degeneration, but the nature of this instability over the time course of disease development is not well understood. The goal of this study was to characterize three-dimensional motion of the canine knee during gait, before and serially for two years after ACL transection. Canine tibial-femoral kinematics were assessed during treadmill gait before and serially for two years after ACL transection (ACL-D group; 18 dogs) or sham transection (ACL-I group; five dogs). Kinematic data was collected at 250 frames/s using a biplane video-radiographic system. Six degree-of-freedom motions of the tibia relative to the femur were calculated, and values immediately prior to pawstrike as well as the maximum, minimum, midpoint and range of motion during early/mid stance were extracted. Between-group differences relative to baseline (pre-transection) values, as well as changes over time post-transection, were determined with a repeated-measures ANCOVA. In the ACL-D group, peak anterior tibial translation (ATT) increased by 10 mm (p < 0.001), and did not change over time (p = 0.76). Pre-pawstrike ATT was similar to ACL-intact values early on (2,4 months) but then increased significantly over time, by 3.5 mm (p < 0.001). The range of ab/adduction motion nearly doubled after ACL loss (from 3.3° to 6.1°). The magnitude (midpoint) of knee adduction also increased significantly over time (mean increase 3.0°; p = 0.036). All changes occurred primarily between 6 and 12 months. There were no significant differences between groups in the transverse plane, and no significant changes over time in the ACL-I group. In summary, peak anterior tibial translation and coronal-plane instability increased immediately after ACL loss, and did not improve with time. ATT just prior to pawstrike and mean knee adduction throughout stance became progressively more abnormal with time, with the greatest changes occurring between 6 and 12 months after ACL transection. This may be due to overload failure of secondary restraints such as the medial meniscus, which has been reported to fail in a similar timeframe in the ACL-deficient dog. The relationships between these complex mechanical alterations and the rate of OA development/progression are currently under investigation. © 2004 Published by Elsevier Ltd. on behalf of Orthopaedic Research Society. [source] Joint compression alters the kinematics and loading patterns of the intact and capsule-transected AC jointJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2003Ryan S. Costic High compressive loads are transmitted through the shoulder across the acromioclavicular (AC) joint to the axial skeleton during activities of daily living and can lead to early joint degeneration or instability. The objective of this study was to quantify the effect of joint compression on the biomechanics of the intact and capsule-transected AC joint during application of three loading conditions. A robotic/universal force-moment sensor testing system was utilized to apply an anterior, posterior or superior load of 70 N in combination with 10 or 70 N of joint compression to fresh-frozen cadaveric shoulders (n = 12). The application of joint compression to the intact AC joint decreased the posterior translation in response to a posterior load (,6.6 ± 2.5 vs ,3.7 ± 1.0 mm, p<0.05). Joint compression also decreased the in situ force in the superior AC capsule by 10 N while increasing the joint contact force by 20 N for all loading conditions (p<0.05). The application of joint compression to the capsule-transected AC joint significantly decreased the amount of posterior and superior translation during posterior (,12.7 ± 6.1 vs ,5.5 ± 3.2 mm, p < 0.05) and superior (5.3 ± 2.9 vs 4.2 ± 2.3 mm, p < 0.05) loading, respectively, while significantly increasing the coupled translations (anterior,posterior, superior,inferior or proximal,distal) in all loading conditions (p < 0.05). The joint contact force also significantly increased by 20 N for all loading conditions (p < 0.05). This quantitative data suggests: (1) common surgical techniques such as distal clavicle resection, which initially reduce painful joint contact, may cause unusually high loads to be supported by the soft tissue structures at the AC joint; and (2) compressive loads transmitted across a capsule-transected AC joint could be concentrated over a smaller area due to the increased coupled motion and joint contact force. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Chondroprotective role of the osmotically sensitive ion channel transient receptor potential vanilloid 4: Age- and sex-dependent progression of osteoarthritis in Trpv4 -deficient miceARTHRITIS & RHEUMATISM, Issue 10 2010Andrea L. Clark Objective Mechanical loading significantly influences the physiology and pathology of articular cartilage, although the mechanisms of mechanical signal transduction are not fully understood. Transient receptor potential vanilloid 4 (TRPV4) is a Ca++ -permeable ion channel that is highly expressed by articular chondrocytes and can be gated by osmotic and mechanical stimuli. The goal of this study was to determine the role of Trpv4 in the structure of the mouse knee joint and to determine whether Trpv4,/, mice exhibit altered Ca++ signaling in response to osmotic challenge. Methods Knee joints of Trpv4,/, mice were examined histologically and by microfocal computed tomography for osteoarthritic changes and bone structure at ages 4, 6, 9, and 12 months. Fluorescence imaging was used to quantify chondrocytic Ca++ signaling within intact femoral cartilage in response to osmotic stimuli. Results Deletion of Trpv4 resulted in severe osteoarthritic changes, including cartilage fibrillation, eburnation, and loss of proteoglycans, that were dependent on age and male sex. Subchondral bone volume and calcified meniscal volume were greatly increased, again in male mice. Chondrocytes from Trpv4+/+ mice demonstrated significant Ca++ responses to hypo-osmotic stress but not to hyperosmotic stress. The response to hypo-osmotic stress or to the TRPV4 agonist 4,-phorbol 12,13-didecanoate was eliminated in Trpv4,/, mice. Conclusion Deletion of Trpv4 leads to a lack of osmotically induced Ca++ signaling in articular chondrocytes, accompanied by progressive, sex-dependent increases in bone density and osteoarthritic joint degeneration. These findings suggest a critical role for TRPV4-mediated Ca++ signaling in the maintenance of joint health and normal skeletal structure. [source] Alteration of sensory neurons and spinal response to an experimental osteoarthritis pain modelARTHRITIS & RHEUMATISM, Issue 10 2010Hee-Jeong Im Objective To verify the biologic links between progressive cellular and structural alterations within knee joint components and development of symptomatic chronic pain that are characteristic of osteoarthritis (OA), and to investigate the molecular basis of alterations in nociceptive pathways caused by OA-induced pain. Methods An animal model of knee joint OA pain was generated by intraarticular injection of mono-iodoacetate (MIA) in Sprague-Dawley rats, and symptomatic pain behavior tests were performed. Relationships between development of OA with accompanying pain responses and gradual alterations in cellular and structural knee joint components (i.e., cartilage, synovium, meniscus, subchondral bone) were examined by histologic and immunohistologic analysis, microscopic examination, and microfocal computed tomography. Progressive changes in the dynamic interrelationships between peripheral knee joint tissue and central components of nociceptive pathways caused by OA-induced pain were examined by investigating cytokine production and expression in sensory neurons of the dorsal root ganglion and spinal cord. Results We observed that structural changes in components of the peripheral knee joint correlate with alterations in the central compartments (dorsal root ganglia and the spinal cord) and symptomatic pain assessed by behavioral hyperalgesia. Our comparative gene expression studies revealed that the pain pathways in MIA-induced knee OA may overlap, at least in part, with neuropathic pain mechanisms. Similar results were also observed upon destabilization of the knee joint in the anterior cruciate ligament transection and destabilization of the medial meniscus models of OA. Conclusion Our results indicate that MIA-induced joint degeneration in rats generates an animal model that is suitable for mechanistic and pharmacologic studies on nociceptive pain pathways caused by OA, and provide key in vivo evidence that OA pain is caused by central sensitization through communication between peripheral OA nociceptors and the central sensory system. Furthermore, our data suggest a mechanistic overlap between OA-induced pain and neuropathic pain. [source] Ligament and bone pathologic abnormalities more frequent in neuropathic joint disease in comparison with degenerative arthritis of the foot and ankle: Implications for understanding rapidly progressive joint degeneration,ARTHRITIS & RHEUMATISM, Issue 8 2010Jill Halstead Objective The variable disease progression of osteoarthritis (OA) and the basis for rapid joint deterioration in some subgroups of patients are poorly understood. To explore an anatomic basis for rapidly progressive OA, this observational study compared the magnetic resonance imaging (MRI) patterns of disease between patients with neuropathic joint disease (NJD) and patients with degenerative arthritis of the ankle and foot. Methods MR images of the foot and ankle of patients with early NJD (n = 7) and patients with OA (n = 15) were assessed. The anonomized MR images were dichotomously scored by a musculoskeletal radiologist for the presence of the following abnormalities per bone (of a total of 14 bones): cartilage defects, bone cysts, bone marrow edema, fractures, joint debris, joint effusions, tendinopathy, tendinitis, and ligament tears. Results Although the degree of cartilage damage and joint cyst formation was comparable between the groups, the degree of ligament tears, or change in MRI signal intensity in the ligaments, was significantly greater in patients with NJD compared with patients with OA (median of 3 tears versus 0, of 14 total bones; P < 0.01). Moreover, in patients with early NJD compared with patients with OA, there was a significantly greater degree of diffuse bone marrow edema (median of 6.5 tarsal bones versus 2 adjacent bones, of 14 total bones; P < 0.01), a greater number of bone fractures (median 4 versus 0; P < 0.01), and more frequent bone debris (median 4.5 versus 0; P = 0.013). Conclusion This analysis of NJD in the foot and ankle shows the predominance of bone and ligament abnormalities in NJD compared with the pattern of involvement in OA. These findings highlight the importance of structures other than articular cartilage in OA of the ankle and foot, and suggest that rapid joint degeneration in NJD may be more ligamentogenic or osteogenic in nature. [source] Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritisARTHRITIS & RHEUMATISM, Issue 10 2009Timothy M. Griffin Objective To test the hypothesis that obesity resulting from deletion of the leptin gene or the leptin receptor gene results in increased knee osteoarthritis (OA), systemic inflammation, and altered subchondral bone morphology. Methods Leptin-deficient (ob/ob) and leptin receptor,deficient (db/db) female mice compared with wild-type mice were studied, to document knee OA via histopathology. The levels of serum proinflammatory and antiinflammatory cytokines were measured using a multiplex bead immunoassay. Cortical and trabecular subchondral bone changes were documented by microfocal computed tomography, and body composition was quantified by dual x-ray absorptiometry. Results Adiposity was increased by ,10-fold in ob/ob and db/db mice compared with controls, but it was not associated with an increased incidence of knee OA. Serum cytokine levels were unchanged in ob/ob and db/db mice relative to controls, except for the level of cytokine-induced neutrophil chemoattractant (keratinocyte chemoattractant; murine analog of interleukin-8), which was elevated. Leptin impairment was associated with reduced subchondral bone thickness and increased relative trabecular bone volume in the tibial epiphysis. Conclusion Extreme obesity due to impaired leptin signaling induced alterations in subchondral bone morphology without increasing the incidence of knee OA. Systemic inflammatory cytokine levels remained largely unchanged in ob/ob and db/db mice. These findings suggest that body fat, in and of itself, may not be a risk factor for joint degeneration, because adiposity in the absence of leptin signaling is insufficient to induce systemic inflammation and knee OA in female C57BL/6J mice. These results imply a pleiotropic role of leptin in the development of OA by regulating both the skeletal and immune systems. [source] Developmental and osteoarthritic changes in Col6a1 -knockout mice: Biomechanics of type VI collagen in the cartilage pericellular matrixARTHRITIS & RHEUMATISM, Issue 3 2009Leonidas G. Alexopoulos Objective Chondrocytes, the sole cell type in articular cartilage, maintain the extracellular matrix (ECM) through a homeostatic balance of anabolic and catabolic activities that are influenced by genetic factors, soluble mediators, and biophysical factors such as mechanical stress. Chondrocytes are encapsulated by a narrow tissue region termed the "pericellular matrix" (PCM), which in normal cartilage is defined by the exclusive presence of type VI collagen. Because the PCM completely surrounds each cell, it has been hypothesized that it serves as a filter or transducer for biochemical and/or biomechanical signals from the cartilage ECM. The present study was undertaken to investigate whether lack of type VI collagen may affect the development and biomechanical function of the PCM and alter the mechanical environment of chondrocytes during joint loading. Methods Col6a1,/, mice, which lack type VI collagen in their organs, were generated for use in these studies. At ages 1, 3, 6, and 11 months, bone mineral density (BMD) was measured, and osteoarthritic (OA) and developmental changes in the femoral head were evaluated histomorphometrically. Mechanical properties of articular cartilage from the hip joints of 1-month-old Col6a1,/,, Col6a1+/,, and Col6a1+/+ mice were assessed using an electromechanical test system, and mechanical properties of the PCM were measured using the micropipette aspiration technique. Results In Col6a1,/, and Col6a1+/, mice the PCM was structurally intact, but exhibited significantly reduced mechanical properties as compared with wild-type controls. With age, Col6a1,/, mice showed accelerated development of OA joint degeneration, as well as other musculoskeletal abnormalities such as delayed secondary ossification and reduced BMD. Conclusion These findings suggest that type VI collagen has an important role in regulating the physiology of the synovial joint and provide indirect evidence that alterations in the mechanical environment of chondrocytes, due to either loss of PCM properties or Col6a1,/, -derived joint laxity, can lead to progression of OA. [source] | ||||||||||