Minority Supplement for Mr. Julian Vallejo to obtain a Ph.D. Abstract of PPG Our society is becoming more and more sedentary, thereby worsening and accelerating the effects of aging. The central system that is responsible for the beneficial effects of mobility on brain function, cardiac function, metabolism, and other organs is the musculoskeletal system. Without muscle contraction and bone movement, there is no exercise and therefore no beneficial effects on the organism. Exercise appears to delay the negative effects of aging and can ameliorate negative effects of diseases associated with aging. Exercise maintains both muscle and bone mass and it is most likely the maintenance of the health of the musculoskeletal system that is responsible for the health of the organism. The hypothesis to be tested includes: Crosstalk occurs between muscle and bone through systemic factors. The osteocyte is regulated by both mechanical loading and by factors secreted by contracted muscle. In turn, the osteocyte regulates muscle myogenesis and function. Exercise targets the osteocyte and muscle by reducing the negative effects of aging.
The specific aims of this program project renewal are 1). Determine how young and old osteocytes regulate myogenesis, muscle mass and function, 2). Determine how muscle protects and maintains osteoblast/osteocyte viability and function, 3). Examine the role of extracellular vesicles in bone-muscle crosstalk, 4). Determine the role of estrogen/?-catenin in muscle-bone crosstalk with aging and 5). Determine if exercise can rescue or reduce the negative effects of aging on bone-muscle crosstalk.
These specific aims will be accomplished through a multidisciplinary approach where bone and muscle biologists interact along with engineers and biochemists. This program project focuses on bone-muscle crosstalk utilizing muscle and bone transgenic mouse models, unique bone and muscle cell lines, live cell imaging and intravital imaging capabilities and integration of metabolomics and lipidomics. The projects and their supporting cores are highly integrative and will lead to synergistic interactions where the potential for progress and success is greater than the individual components. Identification of the mechanisms used by muscle and bone to communicate and regulate the musculoskeletal system as a whole and how these are regulated by exercise should lead to interventions for musculoskeletal disease, dysfunction, and disorders and prevent the negative effects of immobilization and aging, not only on the musculoskeletal system, but on the overall health of the individual.
This program project renewal will continue to identify the molecular mechanisms whereby bone and muscle communicate independent of mechanical loading of bone by muscle. The underlying premise for these studies is that bone cells secrete circulatory factors that regulate muscle mass and function and in turn, secreted factors from contracted muscle can maintain bone cell viability and function. The negative effects of aging on this ?muscle-bone crosstalk? are attenuated by normal physiological exercise. Identification of these molecular mechanisms should lead to therapeutics for the twin condition of ?osteo-sarcopenia?.
|Bonewald, Lynda (2018) Use it or lose it to age: A review of bone and muscle communication. Bone 120:212-218|
|Kitase, Yukiko; Vallejo, Julian A; Gutheil, William et al. (2018) ?-aminoisobutyric Acid, l-BAIBA, Is a Muscle-Derived Osteocyte Survival Factor. Cell Rep 22:1531-1544|
|Pin, Fabrizio; Barreto, Rafael; Kitase, Yukiko et al. (2018) Growth of ovarian cancer xenografts causes loss of muscle and bone mass: a new model for the study of cancer cachexia. J Cachexia Sarcopenia Muscle 9:685-700|
|Morris, Josephine L; Cross, Stephen J; Lu, Yinhui et al. (2018) Live imaging of collagen deposition during skin development and repair in a collagen I - GFP fusion transgenic zebrafish line. Dev Biol 441:4-11|
|Jähn, Katharina; Kelkar, Shilpa; Zhao, Hong et al. (2017) Osteocytes Acidify Their Microenvironment in Response to PTHrP In Vitro and in Lactating Mice In Vivo. J Bone Miner Res 32:1761-1772|
|Huang, Jian; Romero-Suarez, Sandra; Lara, Nuria et al. (2017) Crosstalk between MLO-Y4 osteocytes and C2C12 muscle cells is mediated by the Wnt/?-catenin pathway. JBMR Plus 1:86-100|
|Bonewald, Lynda F (2017) The Role of the Osteocyte in Bone and Nonbone Disease. Endocrinol Metab Clin North Am 46:1-18|
|Vemula, Harika; Kitase, Yukiko; Ayon, Navid J et al. (2017) Gaussian and linear deconvolution of LC-MS/MS chromatograms of the eight aminobutyric acid isomers. Anal Biochem 516:75-85|
|Begonia, Mark; Dallas, Mark; Johnson, Mark L et al. (2017) Comparison of strain measurement in the mouse forearm using subject-specific finite element models, strain gaging, and digital image correlation. Biomech Model Mechanobiol 16:1243-1253|
|Tiede-Lewis, LeAnn M; Xie, Yixia; Hulbert, Molly A et al. (2017) Degeneration of the osteocyte network in the C57BL/6 mouse model of aging. Aging (Albany NY) 9:2190-2208|
Showing the most recent 10 out of 39 publications