The dog is a common model for study of osteoarthritis (OA). Subjective histologic scoring systems have often served as the reference standard for presence and severity of OA. However, these scoring systems have perceived shortcomings. The system developed for this report attempts to address these shortcomings by providing a standardized methodology for global assessment of the joint, versatility and the potential for relative weighting of pathology, allowing for comparison among time points, studies, and centers, and critical analysis of the system's reliability. The proposed system for assessment of canine tissues appears to provide an effective method for global assessment of articular pathology in OA. The system is versatile, comprehensive, and reliable and appears to have advantages over conventional scoring systems.
Objective. To investigate the development of osteoarthritis (OA) after transection of the medial collateral ligament and partial medial meniscectomy in mice in which genes encoding either interleukin-1 (IL-1), IL-1-converting enzyme (ICE), stromelysin 1, or inducible nitric oxide synthase (iNOS) were deleted.Methods. Sectioning of the medial collateral ligament and partial medial meniscectomy were performed on right knee joints of wild-type and knockout mice. Left joints served as unoperated controls. Serial histologic sections were obtained from throughout the whole joint of both knees 4 days or 1, 2, 3, or 4 weeks after surgery. Sections were graded for OA lesions on a scale of 0-6 and were assessed for breakdown of tibial cartilage matrix proteoglycan (aggrecan) and type II collagen by matrix metalloproteinases (MMPs) and aggrecanases with immunohistochemistry studies using anti-VDIPEN, anti-NITEGE, and Col2-3/4C short neoepitope antibodies. Proteoglycan depletion was assessed by Alcian blue staining and chondrocyte cell death, with the TUNEL technique.Results. All knockout mice showed accelerated development of OA lesions in the medial tibial cartilage after surgery, compared with wild-type mice. ICE-, iNOS-, and particularly IL-1-knockout mice developed OA lesions in the lateral cartilage of unoperated limbs. Development of focal histopathologic lesions was accompanied by increased levels of MMP-, aggrecanase-, and collagenase-generated cleavage neoepitopes in areas around lesions, while nonlesional areas showed no change in immunostaining. Extensive cell death was also detected by TUNEL staining in focal areas around lesions.Conclusion. We postulate that deletion of each of these genes, which encode molecules capable of producing degenerative changes in cartilage, leads to changes in the homeostatic controls regulating the balance between anabolism and catabolism, favoring accelerated cartilage degeneration. These observations suggest that these genes may play important regulatory roles in maintaining normal homeostasis in articular cartilage matrix turnover.Osteoarthritis (OA) is a degenerative condition characterized by loss of articular cartilage and joint remodeling. The degradation of cartilage is characterized by increased expression of matrix metalloproteinases (MMPs), cytokines including interleukin-1 (IL-1) and tumor necrosis factor ␣ (TNF␣) and their receptors, and nitric oxide synthase (NOS) (1). Aging mice present Supported by the Arthritis Research Campaign (UK).
When lameness occurs in a load-bearing limb, compensatory load adjustments are made in the other supporting limbs. The vertical component of the ground reaction force, as measured by force platform analysis, reflects these adjustments. This study describes the pattern of vertical ground reaction force redistribution during experimental, chronic hindlimb lameness in dogs. The peak and impulse of the vertical ground reaction force were measured and described in 13 dogs before, and at 2, 6, and 12 weeks after transection of the cranial cruciate ligament. These variables were compared among limbs. The vertical ground reaction force in the forelimbs did not change significantly during the course of the study. At 2, 6, and 12 weeks after surgery, means of peak vertical force in the limb that underwent surgery were 18.9%, 44.0%, and 61.3% respectively, of presurgical values. In the contralateral limb, corresponding values were 131.7%, 112.8% and 112.9% respectively. If one accepts the relationship of mechanical loading to musculoskeletal architecture and the now certain relationship between lameness and compensatory loading of other limbs, then the use of another limb of the same animal as a control is a potential study design flaw.
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