The Histology, Biochemistry, and Molecular Imaging (HBMI) Core of the University of Rochester Resource- based Center for Bone, Muscle and Orthopaedic Research (ROCSTARR) will provide histopathology, histomorphometry, biochemistry, and cellular and molecular imaging and analysis services and state-of-the-art resources and training to support clinical and basic research in the Center for Musculoskeletal Research (CMSR) under the leadership of Drs. Boyce and Anolik. It has 4 research and service Sub-Cores: 1) Histology & Immunohistochemistry; 2) Microscopy, Histomorphometry & 3-D Tissue Clearing/Imaging; 3) Biochemistry, Cellular, Molecular, & Single Cell Omics; and 4) Small Animal Surgery and Support. Skilled Sub-Core ROCSTARR advisors and lab technicians will provide training in use of sophisticated instruments and techniques within each Sub-Core. The Core will integrate these services and resources and advance understanding of how biochemical and molecular signals and cellular responses to inflammation, regeneration and repair affect MSK tissues. It will also accelerate advances in basic research findings to clinical practice. The Core will develop new techniques that will continue to transform understanding of MSK developmental and disease processes in animals and humans. The expansion and integration of services within the HBMI Core will further increase productivity, enhance the efficiency of the Core, enable the translation between histologic and histomorphometric data and the underlying cellular and molecular mechanisms in musculoskeletal diseases and accelerate the pace of research for all funded projects within the CMSR. The Specific Aims of the Core for all ROCSTARR investigators and their collaborators are to: 1) provide cost-efficient and high- quality histology, IHC, imaging, and histomorphometry services; 2) provide ROCSTARR faculty and their collaborators access to state-of-the-art molecular biochemical, cellular, and molecular analytics, including new single cell transcriptomic platforms on dissociated cells and bioinformatics pipelines, and to help train students and post-docs to use HBMI standard operating procedures; 3) provide expertise and mentorship to our New/Early Stage Investigators by integrating staff and expert ROCSTARR faculty as Advisors in specialty Sub- Cores to offer conceptual and technical guidance on cutting edge histologic, imaging, biochemical, and molecular technologies; and 4) advance MSK basic, translational and clinical research by: a) providing whole slide imaging technology and developing automated analysis of histomorphometric parameters of MSK tissues with Visiopharm image analysis software; b) expanding access to multiplexed histology platforms (mass cytometry and immunofluorescence); c) applying novel deep tissue high-spatial imaging platforms, including tissue clearing, electron microscopy and 3D reconstruction to MSK tissue; d) developing protocols for single cell transcriptomics, isolation of high ...