Arthroscopy -- a potential "gold standard" for the diagnosis of the chondropathy of early osteoarthritis.
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OBJECTIVES: The aims of this study were to: 1. Evaluate the performance of arthroscopy for the diagnosis of chondropathy and to compare it to that of direct non-arthroscopic assessments; 2. Determine intra-observer reliability of arthroscopic assessments; 3. Evaluate the effects of the arthroscopic video quality and probing upon diagnostic performance. DESIGN: The ovine medial meniscectomy (MMx) model of early osteoarthritis (OA) was used assuming that pre-MMx articular cartilage (AC) was "normal" and post-MMx AC "chondropathic". Video recordings of arthroscopic assessments of each stifle compartment were evaluated. Scores were given for the quality of the video and the amount of probing. The diagnostic performances of dynamic shear modulus (G), light microscopic assessment and superficial zone collagen birefringence assessments were evaluated and compared to that of arthroscopy. Intra-observer reliability of arthroscopic assessments was also evaluated. RESULTS: Arthroscopic assessments had high sensitivity (91-100%), specificity (62-88%) and accuracy (75-93%) for the diagnosis of chondropathy 16 weeks after MMx. Arthroscopy compared favourably with the direct non-arthroscopic assessments in the lateral compartment and was found to have extremely high intra-observer reliability (kappa 0.78-1.00). The quality of arthroscopic video recordings and the amount of probing did not significantly influence accuracy or reliability. CONCLUSIONS: Arthroscopy performs as well as direct non-arthroscopic assessments of AC for diagnosis of early OA. These results suggest that arthroscopy can be used as a "gold standard" for the validation of non-invasive assessments like magnetic resonance imaging and that arthroscopic diagnosis can be based on small amounts of video footage without AC probing. (+info)
A new biotechnology for articular cartilage repair: subchondral implantation of a composite of interconnected porous hydroxyapatite, synthetic polymer (PLA-PEG), and bone morphogenetic protein-2 (rhBMP-2).
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OBJECTIVE: Articular cartilage repair remains a major obstacle in tissue engineering. We recently developed a novel tool for articular cartilage repair, consisting of a triple composite of an interconnected porous hydroxyapatite (IP-CHA), recombinant human bone morphogenetic protein-2 (rhBMP-2), and a synthetic biodegradable polymer [poly-d,l-lactic acid/polyethylene glycol (PLA-PEG)] as a carrier for rhBMP-2. In the present study, we evaluated the capacity of the triple composite to induce the regeneration of articular cartilage. METHODS: Full-thickness cartilage defects were created in the trochlear groove of 52 New Zealand White rabbits. Sixteen defects were filled with the bone morphogenetic protein (BMP)/PLA-PEG/IP-CHA composite (group I), 12 with PLA-PEG/IP-CHA (group II), 12 with IP-CHA alone (group III), and 12 were left empty (group IV). The animals were killed 1, 3, and 6 weeks after surgery, and the gross appearance of the defect sites was assessed. The harvested tissues were examined radiographically and histologically. RESULTS: One week after implantation with the BMP/PLA-PEG/IP-CHA composite (group I), vigorous repair had occurred in the subchondral defect. It contained an agglomeration of mesenchymal cells which had migrated from the surrounding bone marrow either directly, or indirectly via the interconnecting pores of the IP-CHA scaffold. At 6 weeks, these defects were completely repaired. The regenerated cartilage manifested a hyaline-like appearance, with a mature matrix and a columnar organization of chondrocytes. CONCLUSIONS: The triple composite of rhBMP-2, PLA-PEG, and IP-CHA promotes the repair of full-thickness articular cartilage defects within as short a period as 3 weeks in the rabbit model. Hence, this novel cell-free implant biotechnology could mark a new development in the field of articular cartilage repair. (+info)
Bilateral dystrophic ossification of the thyroid cartilage appearing as symmetrical laryngeal masses.
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Primary cartilaginous lesions of the larynx are relatively uncommon. We present a case of bilaterally pseudocystic lesion of the thyroid cartilage that demonstrated progressive calcification. Pathologic analysis showed features suggesting a dystrophic lesion with no evidence of malignancy. We hypothesize that repetitive microtrauma related to muscular overuse probably led to inflammatory changes at tendinous insertions on the laryngeal cartilage and resulted in dystrophic ossification of the laryngeal cartilage. (+info)
Histone deacetylases--a new target for suppression of cartilage degradation?
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Increased expression of metalloproteinases is a fundamental aspect of arthritispathology and its control is a major therapeutic objective. In cartilage cultured in the presence of the cytokines interleukin-1 and oncostatin M, chondrocytes produce enhanced levels of metalloproteinases of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) and MMP (matrix metalloproteinase) families, resulting in the degradation of aggrecan and collagen. The histone deacetylase inhibitors trichostatin A and butyrate were shown to drastically reduce expression of these enzymes relatively selectively, with concomitant inhibition of breakdown of matrix components. This family of enzymes is therefore a promising target for therapeutic intervention. (+info)
Patellofemoral joint biomechanics and tissue engineering.
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Recent advances in the study of patellofemoral joint biomechanics have provided promising diagnosis and treatment modalities for patellofemoral joint disorders, such as quantitative assessment of cartilage lesions from noninvasive imaging, computer simulations of surgical procedures for optimizing surgical parameters and potentially predicting outcomes, and cartilage tissue engineering for the treatment of advanced degenerative joint disease. These technologies are still in development and their clinical potentials remain an ongoing topic of investigation. We review some of our progress in addressing these issues, and the important role of cartilage mechanics and lubrication in understanding the challenges regarding patellofemoral surgery and cartilage tissue engineering. (+info)
Evidence of a major gene from Bayesian segregation analyses of liability to osteochondral diseases in pigs.
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Bayesian segregation analyses were used to investigate the mode of inheritance of osteochondral lesions (osteochondrosis, OC) in pigs. Data consisted of 1163 animals with OC and their pedigrees included 2891 animals. Mixed-inheritance threshold models (MITM) and several variants of MITM, in conjunction with Markov chain Monte Carlo methods, were developed for the analysis of these (categorical) data. Results showed major genes with significant and substantially higher variances (range 1.384-37.81), compared to the polygenic variance (sigmau2). Consequently, heritabilities for a mixed inheritance (range 0.65-0.90) were much higher than the heritabilities from the polygenes. Disease allele frequencies range was 0.38-0.88. Additional analyses estimating the transmission probabilities of the major gene showed clear evidence for Mendelian segregation of a major gene affecting osteochondrosis. The variants, MITM with informative prior on sigmau2, showed significant improvement in marginal distributions and accuracy of parameters. MITM with a "reduced polygenic model" for parameterization of polygenic effects avoided convergence problems and poor mixing encountered in an "individual polygenic model." In all cases, "shrinkage estimators" for fixed effects avoided unidentifiability for these parameters. The mixed-inheritance linear model (MILM) was also applied to all OC lesions and compared with the MITM. This is the first study to report evidence of major genes for osteochondral lesions in pigs; these results may also form a basis for underpinning the genetic inheritance of this disease in other animals as well as in humans. (+info)
Osteoarthritis and meniscus disorders of the knee as occupational diseases of miners.
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AIM: To determine whether kneeling or squatting for prolonged periods is sufficiently causally associated with an increased risk of injury or degenerative disease of the knee joint as to meet the classic criteria to be considered an occupational disease of coal miners for whom these are or have been routine working postures. METHOD: Systematic literature searches were made for studies relating to kneeling and squatting as part of the working environment of coal mines and the role of these postures in causation of knee disorders in coal miners, analogous occupations, populations, and communities. The working environment and potentially damaging forces on the knee when kneeling or squatting were described. Papers on the incidence or prevalence of knee disorders in occupational and other groups were scored against five criteria independently by each author, and from this a single consensus score representing the overall strength of evidence given by the research was awarded. The evidence was then weighed against the criteria for an occupational disease. RESULTS: Nineteen published papers were scored, the majority of which focussed on osteoarthritis as the outcome of interest. Few of the studies found focussed specifically on miners, and those that did tended to involve small numbers of subjects and were carried out before 1960, when the mining population was at its largest but epidemiological evidence of the risk factors for knee disorders was not well established. The non-mining studies in the review represent groups of workers with a similar or lesser kneeling content in their work. CONCLUSION: The papers reviewed provide sufficient evidence to conclude that work involving kneeling and/or squatting is causally associated with an increased risk of osteoarthritis of the knee. In some of the more recent epidemiologically sound studies, frequent or prolonged kneeling or squatting doubles the general risk of osteoarthritis of the knees found in the general population. This may be of particular importance in welfare and medico-legal situations. There was also evidence to suggest that lifting, in combination with kneeling/squatting, an activity also performed by miners in the course of their work, is associated with an excess risk of osteoarthritis above that attributed to kneeling/squatting alone. (+info)
Bone morphogenetic proteins: from structure to clinical use.
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Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the transforming growth factor ss superfamily. Family members are expressed during limb development, endochondral ossification, early fracture, and cartilage repair. The activity of BMPs was first identified in the 1960s but the proteins responsible for bone induction were unknown until the purification and cloning of human BMPs in the 1980s. To date, about 15 BMP family members have been identified and characterized. The signal triggered by BMPs is transduced through serine/threonine kinase receptors, type I and II subtypes. Three type I receptors have been shown to bind BMP ligands, namely: type IA and IB BMP receptors and type IA activin receptors. BMPs seem to be involved in the regulation of cell proliferation, survival, differentiation and apoptosis, but their hallmark is their ability to induce bone, cartilage, ligament, and tendon formation at both heterotopic and orthotopic sites. This suggests that, in the future, they may play a major role in the treatment of bone diseases. Several animal studies have illustrated the potential of BMPs to enhance spinal fusion, repair critical-size defects, accelerate union, and heal articular cartilage lesions. Difficulties in producing and purifying BMPs from bone tissue have prompted the attempts made by several laboratories, including ours, to express these proteins in the recombinant form in heterologous systems. This review focuses on BMP structure, molecular mechanisms of action and significance and potential applications in medical, dental and veterinary practice for the treatment of cartilage and bone-related diseases. (+info)