PROJECT SUMMARY/ABSTRACT The mechanical environment is a foundational input to the proper development, composition, and function of the musculoskeletal system. Probing the integrity of mechanical signaling mechanisms in bone and muscle require very specialized techniques, expertise, and instrumentation, all of which have been a hallmark of the IU bone group for many years. This application describes the creation, scope, operation, and administration of a unique core facility, housed within the newly created Indiana Center for Musculoskeletal Biology (ICMH), that provides dedicated infrastructure to support investigators in the area of mechanobiology for in vivo and in vitro applications. The core is directed by Dr. Alex Robling and co-directed by Dr. Joey Wallace, who bring considerable experience and breadth to the core leadership. The core will offer services related to in vivo skeletal loading, in vivo muscle loading, in vivo disuse experiments (for both bone and muscle), in vitro mechanotransduction models, and development of new techniques to move the field forward. Training and outreach components are included, to bring more investigators into the field and to educate those who wish to mechanobiology approaches into their lab as standard practice. Aim 1: Provide in vivo bone and muscle mechanotransduction services, including anabolic (ulnar loading, tibia loading, muscle electrostimulation, vibration, treadmill), and catabolic (tail suspension, Botox paralysis, immobilization) techniques. Aim 2: Provide in vitro bone and muscle cellular mechanotransduction services, including parallel plate fluid flow and substrate strain techniques for cultured bone and muscle cells from a variety of sources (e.g., CRISPR-targeted cell lines, primary cells from mutant mice, transfected/infected cells, drug-treated cells). Aim 3: Provide training and education in the use and interpretation of mechanobiology models, including theory, application, technical constraints, and advice on next steps, to investigators, with the goal of increasing the awareness of mechanobiological approaches to MSK-related research questions. Aim 4: Innovate and advance the mechanobiology field in technical aspects of research strategy and tools, so that current and future investigators have a greater selection of appropriate models to test more focused hypotheses related to mechanobiology. In summary, this core will support the existing, highly experienced investigators, will train new investigators in these approaches, and will offer services to those that had not previously considered these technologies to address their scientific questions and expedite discovery of treatments and therapies for MSK diseases.