Summary/Abstract - Overall One in two adults in the United States has a prevalent musculoskeletal condition, with related costs of $900 billion annually. To address this crisis, efficient utilization of resources and sustained commitment to basic and translational research are essential. We propose the Washington University Resource-Based Center for Musculoskeletal Biology and Medicine, dedicated to two long-term goals – to advance research on the biological basis of musculoskeletal disease, and to develop and test biologically based intervention strategies. We represent a dynamic Research Community of 81 investigators, affiliated with 17 academic departments. Since 2009, the Center has contributed to 343 publications that have been cited 6687 times. The annual external funding of Center investigators is $66.2 million, including $8.1 million from NIAMS. Our work focuses on the most prevalent and costly musculoskeletal disorders – arthritis, back pain, bone and joint trauma, osteoporosis, and metastatic cancer. Notably, the majority of our research endeavors are in basic and pre-clinical studies. Therefore, our overall objective is to support the Research Community in the development, implementation and evaluation of animal models for musculoskeletal biology and medicine. We will address this objective through four integrated Aims. Aim 1. Through an Administrative Core (A), provide Center leadership to manage the Cores and engage in outreach. Direct an Enrichment Program that will foster the development of the next generation of musculoskeletal investigators through a Pilot & Feasibilty program, seminars, symposia and other activities. Aim 2. Through the Musculoskeletal Structure and Strength Core (B), support access, training and cost-effective utilization for: i) x-ray based imaging methods to quantify morphology, and ii) biomechanical methods to quantify mechanical properties of musculoskeletal tissues (bone, tendon, muscle, cartilage, disc). Aim 3. Through the Musculoskeletal Histology and Morphometry Core (C), perform tissue processing, embedding, sectioning and staining, protocol maintenance and user training appropriate for the range of tissues/techniques required in musculoskeletal research. Support access and training for routine and advanced microscopy and histomorphometry. Aim 4. In the Animal Models of Joint Injury and Disease Core (D), provide training and implementation for reproducible mouse models of osteoarthritis and rheumatoid arthritis. Measure in vivo biomechanics and behavior to assess joint pain and function. Create a repository of tissue and serum samples from arthritic mouse models. In summary, the four Cores we propose will provide essential support for our Research Community to develop, implement and evaluate animal models for musculoskeletal biology and medicine. A common theme for each Core is to support training and enrichment activities to foster development of the next generation of musculoskeletal investigators.