Initial evidence for the involvement of bone morphogenetic protein-2 early during periosteal chondrogenesis.

ABSTRACT

The potential of periosteum to form cartilage makes periosteal transplantation a viable approach to repairing defects in articular cartilage, which has a limited potential for repair. However, cartilage repair, including that by periosteal chondrogenesis, is poorly understood. Consequently, a thorough understanding of its molecular mechanisms will help to achieve the quality of neocartilage required for its clinical application in damaged joints. An in vitro model was used to study the early molecular events of periosteal chondrogenesis. During the search for the expression of transforming growth factor-beta-related mRNAs in this model system, bone morphogenetic protein-2 mRNA expression was found to be upregulated 20-fold within the first 12 hours of culture. This stimulation was dependent on the explants being suspended in agarose and did not occur with explants cultured in liquid medium. The upregulation of bone morphogenetic protein-2 mRNA expression was also enhanced by exogenously added transforming growth factor-beta1 in the presence of fetal calf serum. The upregulation, however, was not transient; rather, it persisted over a prolonged period in both transforming growth factor-beta1-treated and untreated explants. Further data indicate that this stimulation of bone morphogenetic protein-2 mRNA expression was regulated at the transcriptional level and that no new protein synthesis was required for this. Bone morphogenetic protein-2 is known to influence developmental chondrogenesis; therefore, these observations direct our attention toward an important potential role of it as a regulator of the early events in cartilage repair. Furthermore, because periosteum produces fracture (cartilage) callus, these findings may be important in defining the molecular mechanisms of fracture healing.