This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In the first project, Dr. Farach-Carson proposes to define precisely the structural and functional roles that perlecan (Pln) and its associated heparan sulfate (HS) proteoglycan chains play in cartilage biology. HS proteoglycans have recently emerged as key regulators of cartilage biology and play critical roles during embryonic development, in maintenance of cartilage structures in the adult organism, and in regrowth of damaged cartilage resulting from age, osteoarthritis or injury. Using a combination of in vitro chondrogenesis models and mice harboring mutations in Pln or HS biosynthetic enzymes, Dr. Farach-Carson et al. will address the hypothesis that Pln and heparanase I are essential players in normal chondrogenesis and cartilage healing, and that their complex roles in these processes are associated with specialized functions encrypted within the various domains and require the presence and turnover of HS. Dr. Farach-Carson is a full professor and will not have a mentor.