Extensive laboratory and surgical experience by the Principal Investigator has proven that cartilage regeneration and biological resurfacing of damaged joints is possible using periosteal grafts. However, the major limitation is an age-dependent decrease in the potential of periosteum to produce cartilage in subjects beyond early adulthood. The next step is to document age-related changes in the cellular events in periosteal chondrogenesis and factors regulating patients. The periosteal explant culture model developed by the Principal Investigator makes it now possible to pose and test, in vitro, a logical series of hypotheses to achieve this objective. In Specific Aim 1, it will be determined if the age-dependent decrease in chondrogenic potential of the periosteum correlates with changes in chondrocyte precursor cell frequency, proliferation and/or differentiation. Specific Aim 2 will focus on regulation of proliferation, testing the hypothesis that growth hormone (GH) and insulin-like growth factor (IGF-1) regulate proliferation of chondrocyte precursors in the periosteum. Next, Specific Aim 3 will test the validity of our model, that proliferation and differentiation are sequence-dependent, permitting more accurate timing of the study or control of either of these events. Finally, in Specific Aim 4, it will be determined if the age-dependent chondrogenic potential of the periosteum is related to altered activity of certain growth factors (or their receptors) known to regulate chrondrocytes, IGF-1 and TGF-beta, will be determined. The impact of society and the improvement in the quality of life for so many thousands of patients suffering from, or at risk of developing, arthritis would be profound if arthritis could be prevented in many, and treated in others, with biological resurfacing.