6 Growth Factors and Chondrogenesis

Chondrogenesis, whether during the formation of cartilage models during endochondral bone formation, longitudinal and apositional growth, maintenance of the articular surfaces, or during repair and healing, is a carefully orchestrated multistep process. As such, regulation of this process requires the interplay of a large number of factors, including inductive cues from surrounding tissues, intercellular signals emanating from within the cartilage itself, and intrinsic factors within the chondrocytes. Indeed, intrinsic and extrinsic regulation are intimately related to one another. In response to specific sets of growth factors, cells at various stages of chondrogenic differentiation activate expression of unique sets of transcription factors committing them to, and defining, particular cell states. In turn, a consequence of the expression of these transcription factors is the regulated production of stage-specific secreted proteins that feedback on other chondrogenic cells. Of equal importance, the transcriptional state of cells in the chondrogenic pathway determines their ability to respond to specific factors and the nature of their response. These intrinsic and extrinsic factors are thus components of a complex integrated network, a fact that must be borne in mind while considering any one aspect of chondrogenic regulation. Nonetheless, given the incomplete nature of our current understanding of chondrogenesis, and the complexity of the problem, it is perhaps easiest to organize a discussion of chondrogenesis by considering inductive factors and intrinsic regulation individually. This review focuses on the secreted proteins and signal transduction systems that regulate various aspects of chondrogenesis, while the transcription factors upstream and downstream of these...