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. This proposal utilizes a genetically modified mouse model to explore the biological mechanisms underlying non-inflammatory joint degeneration (osteoarthritis). Although late-stage inflammatory events have been more thoroughly investigated, the initial causes of joint degeneration in osteoarthritis are unknown. Some of the causes of osteoarthritis may lie within the complex regulatory networks that orchestrate the events of development and growth of the skeleton early in life. Utilizing newly acquired information about collagen type XI and a newly developed genetically modified mouse line, we will characterize the Col11a1DVR mouse, which may reveal a new level of understanding of skeletal development and disease progression in osteoarthritis. Improved diagnosis and treatment of osteoarthritis will likely result from a more thorough understanding of factors that lead to a predisposition for the development of osteoarthritis early in life, such as those that regulate fibrillogenesis or coordinate the replacement of cartilage by bone. Evidence suggests that Col11a1 is essential in these processes. These studies may give us insight into targets for future preventive and therapeutic strategies.