title: An in vitro model for the pathological degradation of articular cartilage in osteoarthritis.
abstract: The objective of this study was to develop an in vitro cartilage degradation model that emulates the damage seen in early-stage osteoarthritis. To this end, cartilage explants were collagenase-treated to induce enzymatic degradation of collagen fibers and proteoglycans at the articular surface. To assess changes in mechanical properties, intact and degraded cartilage explants were subjected to a series of confined compression creep tests. Changes in extracellular matrix structure and composition were determined using biochemical and histological approaches. Our results show that collagenase-induced degradation increased the amount of deformation experienced by the cartilage explants under compression. An increase in apparent permeability as well as a decrease in instantaneous and aggregate moduli was measured following collagenase treatment. Histological analysis of degraded explants revealed the presence of surface fibrillation, proteoglycan depletion in the superficial and intermediate zones and loss of the lamina splendens. Collagen cleavage was confirmed by the Col II-3/4Cshort antibody. Degraded specimens experienced a significant decrease in proteoglycan content but maintained total collagen content. Repetitive testing of degraded samples resulted in the gradual collapse of the articular surface and the compaction of the superficial zone. Taken together, our data demonstrates that enzymatic degradation with collagenase can be used to emulate changes seen in early-stage osteoarthritis. Further, our in vitro model provides information on cartilage mechanics and insights on how matrix changes can affect cartilage's functional properties. More importantly, our model can be applied to develop and test treatment options for tissue repair.
authors.affiliation: Laboratory for Soft Tissue Research, Tissue Engineering, Regeneration and Repair Program, The Hospital for Special Surgery, New York, NY 10021, United States. Electronic address: GrenierS@hss.edu.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Grenier
authors.affiliation: Laboratory for Soft Tissue Research, Tissue Engineering, Regeneration and Repair Program, The Hospital for Special Surgery, New York, NY 10021, United States.
authors.forename: Madhu M
authors.initials: MM
authors.lastname: Bhargava
authors.affiliation: Laboratory for Soft Tissue Research, Tissue Engineering, Regeneration and Repair Program, The Hospital for Special Surgery, New York, NY 10021, United States.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Torzilli
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D002356:Cartilage / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000494:pharmacology; D019245:Compressive Strength / Q000502:physiology; D018450:Disease Progression; D055119:Elastic Modulus / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D008954:Models, Biological; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D011509:Proteoglycans / Q000378:metabolism; D046509:Tissue Culture Techniques; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D011509:Proteoglycans; D003094:Collagen; D017364:Collagenases
keywords: Articular cartilage; Collagenase; Mechanical properties; Osteoarthritis