Aging sarcopenia is a multifaceted health problem that is further complicated since sarcopenia and osteoporosis are normally related or simultaneous conditions. The current interpretation is that sarcopenia contributes to osteoporosis because muscles, through the loading forces of contraction and stretch, are anabolic stimulators of bones. This view essentially negates the potential for signaling from bone to muscle. Nevertheless, highly innovative, emerging new research has led to the discovery of endocrine functions of bone that could potentially influence muscle through yet unknown mechanisms. The major goal of Subproject 2 is to understand the communication from the osteocyte to muscle, and how aging affects such communication. Our preliminary studies strongly support our concept that bone signals to muscle by modulating muscle myogenic differentiation. Intracellular calcium homeostasis and contractile function. Furthermore, our data now suggests that this bone-muscle signaling Is mediated by the Wnt/b-catenin pathway, and of utmost importance, that this signaling Is compromised during aging. Therefore, we hypothesize that osteocytes signal to muscles via factors that modulate the Wnt/b-catenin pathway and are important for myogenic differentiation, Ca2-*- homeostasis, and contractile function. During aging the signaling from osteocytes to muscles is compromised, thereby contributing to the aging-related decline in muscle function. We will test this hypothesis by tiie following specific aims:
Specific Aim 1 : To determine the molecular mechanisms by which osteocytes modulate muscle myogenic differentiation, and Ca2-i- homeostasis as a function of age.
Specific Aim 2 : To determine how osteocyte factors modulate muscle contractility as a function of age. These studies are the first to propose to systematically investigate the contribution of the Wnt/beta-catenin signaling pathway to the aging decline in muscle function by studying the bone-muscle crosstalk at the cellular and molecular levels. Such knowledge will assist with the identification of new targets for development of therapeutic interventions for sarcopenia and osteoporosis.

Public Health Relevance

Aging sarcopenia (muscle atrophy and weakness) is a serious health problem that afflicts more than 40 million Americans. Sarcopenia is further complicated since sarcopenia and osteoporosis are normally simultaneous conditions. Our studies offer a new interpretation for the effects of bones on muscles and such knowledge will assist with the discovery of new therapeutic interventions for sarcopenia and osteoporosis.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG039355-02
Application #
8460478
Study Section
Special Emphasis Panel (ZAG1-ZIJ-9)
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
2
Fiscal Year
2013
Total Cost
$266,828
Indirect Cost
$88,943
Name
University of Missouri Kansas City
Department
Type
DUNS #
010989619
City
Kansas City
State
MO
Country
United States
Zip Code
64110
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
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
Wang, Zhiying; Bian, Liangqiao; Mo, Chenglin et al. (2017) Targeted quantification of lipid mediators in skeletal muscles using restricted access media-based trap-and-elute liquid chromatography-mass spectrometry. Anal Chim Acta 984:151-161
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

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