Activation of chondrogenesis in response to injury in normal and transgenic mice with cartilage collagen mutations

Objective: The aim of this report is to describe and discuss the reparative capacity of articular cartilage by focusing on similarities and difference s in the activation of chondrogenesis in adult bone and cartilage in respon se to injury. Design: The present report describes three different models of skeletal rep air in the mouse. Two of the models deal with bone healing, where the activ ation of chondrogenesis and formation of callus tissue is greatly dependent on the rigidity of fixation. The third comprises two transgenic mouse mode ls for osteoarthritis where dominant negative mutations in cartilage-specif ic genes disturb the structural integrity of the cartilage collagen fibrils . Results: Molecular biologic and immunohistochemical analyses demonstrated t hat activation of chondrogenesis in healing fractures, i.e., activation and maintenance of the chondrocyte phenotype was preceded by increased product ion and nuclear accumulation of transcription factor SOX9. A similar, albei t smaller, chondrogenic response was observed during healing of biomechanic ally stable metaphyseal bone defects. In degenerating articular cartilage o f transgenic mice, however, the production of cartilage-specific collagen t ypes and SOX9 was markedly reduced upon aging which probably explains why r epair of cartilage defects was insufficient. Conclusion: Understanding of the molecular mechanisms involved in successfu l and unsuccessful activation of chondrogenesis during skeletal repair, wil l provide information needed for enhancement of the chondrocytic response a t sites of skeletal repair. Our data also demonstrates that specific effect or molecules can be efficiently introduced into chondrocytes and their prec ursors by adenovirus-mediated gene transfer. (C) 2001 OsteoArthritis Resear ch Society International.