PROJECT SUMMARY – Overall The NIH has made substantial research investments in response to the large burden of musculoskeletal diseases in the United States. The Washington University Resource-Based Center for Musculoskeletal Biology and Medicine was formed to enhance NIH-funded, musculoskeletal research on our campus, with a focus on basic and pre-clinical research. The Center has profoundly enhanced the musculoskeletal Research Community at WashU and beyond through state-of-the-art Resource Cores and a multifaceted Enrichment Program. Since 2019, our three Resource Cores have supported the work of 155 principal investigators (PIs), including 15 non-WashU PIs. Their work led to 237 publications that have accrued >3,000 citations. We currently represent a diverse Research Community of 97 PIs. The majority (85) are WashU faculty, representing 15 departments. With this renewal application, we aim to increase the impact and inclusiveness of our Center with a new Affiliate Member category targeting investigators in neighboring states who bring added expertise to our Center. Our initial group of Affiliates comprises 12 faculty from six institutions located in five states. In total, the annual extramural funding of our Research Community is $108 million, with $89 million from NIH, of which $13 million is from NIAMS. Our work addresses the most prevalent and costly musculoskeletal disorders – arthritis, back pain, bone and joint trauma, osteoporosis, and metastatic cancer. We have designed the three Resource Cores of the P30 Center to support the critical needs of the Research Community in the development, implementation and evaluation of research models for musculoskeletal biology and medicine. The Administrative Core (A) will provide Center leadership and direct an Enrichment Program. The Musculoskeletal Structure and Strength Core (B) will support access, training and cost-effective utilization for X-ray based imaging methods, and biomechanical methods to quantify mechanical properties of musculoskeletal tissues. The Musculoskeletal Histology and Morphometry Core (C) will perform processing, embedding, sectioning and staining for the range of tissues and techniques required in musculoskeletal research, and support access and training for routine microscopy and histomorphometry, and for advanced microscopy. The Animal Models of Bone & Joint Injury and Disease Core (D) will provide training and hands-on implementation for reproducible mouse models of arthritis (OA, RA) and fracture, and support access and training for state-of-the-art measures of in vivo pain and function. In summary, we propose Cores that will provide essential support for our Research Community to develop, implement, evaluate and interpret research models for musculoskeletal biology and medicine. A common theme for each Core is support for training and instruction to enhance rigor and reproducibility, and for enrichment activities to foster the development of the next generation of m...