Exploring the impact of osteoporosis on myogenesis
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Aging is accompanied by a significant decline in bone mass and strength (osteoporosis) and in muscle mass and strength (sarcopenia). These conditions pose a tremendous threat as each year, one in three older adults living in the community falls. Muscle weakness is a primary risk factor for falls and the associated morbidity and mortality, especially among older adults with osteoporosis. Nurses are aware of the risks and are often in a position to effect a change. For this reason, nurses are positioned to be involved in and to direct research aimed at better understanding these conditions and to make discoveries with translational impact. Until recently, bones and muscles were viewed to function in a mechanical partnership. Emerging research, however, demonstrates a much more complex relationship, resulting not only from mechanical forces, but also from an exchange of biochemical factors. The purpose of this in vitro controlled trial was to explore this biochemical exchange, and investigate the impact of bone factors on skeletal muscle cell differentiation (myogenesis) in the presence of osteoporosis. A series of studies have been completed in mouse models, and our concomitant goal was to expand these studies into humans. Serum used was collected from research subjects in an ongoing case-control study designed to characterize defects in bone quality that contribute to low trauma fractures in postmenopausal women. Using a combination of biophysical, biochemical, and physiological approaches, the serum from subjects with (CASE) and without (CNTRL) osteoporosis was applied to human skeletal muscle cells. The extent of myogenesis in each group was assessed through immunostaining for visualization and calculation of fusion index (i.e., the myogenesis index), flow cytometry for cell cycle analysis, and intracellular calcium measurements for data related to cellular function. Findings from this study will contribute to the growing body of knowledge related to the biochemical communication between bones and muscles, bone-muscle crosstalk. In addition, this study illustrates an excellent opportunity for basic scientists and clinicians to work together to decrease the devastating impact of sarcopenia and osteoporosis.
Table of Contents
Introduction -- Review of literature -- Theoretical framework and methodology -- Results -- Discussion -- Appendix A. IRB Authorization Agreement between UMKC and Creighton University Osteoporosis Research Center -- Appendix B. List of Identified Factors: Exploring the biochemical communication between bones, muscles, and other body tissues -- Appendix C. Human Skeletal Muscle Cells (HSMM) Protocols -- Appendix D. Protocol: Protocol, HSMM, Immunostaining for Fusion Index Calculations -- Appendix E. Protocol: HSMM, Calcium Imaging -- Appendix F. Protocol: HSMM, Flow Cytometry, MUSE™ Cell Cycle Assay -- Appendix G. Data Collected: HSMM, Immunostaining for Fusion Index Calculations -- Appendix H. Data Collected: HSMM, Calcium Imaging -- Appendix I. Data Collected: HSMM, Flow Cytometry for MUSE ™ Cell Cycle Assay -- Appendix J. Comprehensive Tables, Data Collected