The aim of this report is to describe and discuss the reparative capacity of articular cartilage by focusing on similarities and differences in the activation of chondrogenesis in adult bone and cartilage in response to injury.
The present report describes three different models of skeletal repair in the mouse. Two of the models deal with bone healing, where the activation of chondrogenesis and formation of callus tissue is greatly dependent on the rigidity of fixation. The third comprises two transgenic mouse models for osteoarthritis where dominant negative mutations in cartilage-specific genes disturb the structural integrity of the cartilage collagen fibrils.
Molecular biologic and immunohistochemical analyses demonstrated that activation of chondrogenesis in healing fractures, i.e., activation and maintenance of the chondrocyte phenotype was preceded by increased production and nuclear accumulation of transcription factor SOX9. A similar, albeit smaller, chondrogenic response was observed during healing of biomechanically stable metaphyseal bone defects. In degenerating articular cartilage of transgenic mice, however, the production of cartilage-specific collagen types and SOX9 was markedly reduced upon aging which probably explains why repair of cartilage defects was insufficient.
Understanding of the molecular mechanisms involved in successful and unsuccessful activation of chondrogenesis during skeletal repair, will provide information needed for enhancement of the chondrocytic response at sites of skeletal repair. Our data also demonstrates that specific effector molecules can be efficiently introduced into chondrocytes and their precursors by adenovirus-mediated gene transfer.