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    Osteocyte secreted factors inhibit skeletal muscle differentiation.

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    7
    Author
    Wood, CL; Pajevic, PD; Gooi, JH
    Date
    2017-06
    Source Title
    Bone Reports
    Publisher
    Elsevier BV
    University of Melbourne Author/s
    Gooi, Jonathan
    Affiliation
    Biochemistry and Molecular Biology
    Metadata
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    Document Type
    Journal Article
    Citations
    Wood, C. L., Pajevic, P. D. & Gooi, J. H. (2017). Osteocyte secreted factors inhibit skeletal muscle differentiation.. Bone Rep, 6, pp.74-80. https://doi.org/10.1016/j.bonr.2017.02.007.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255603
    DOI
    10.1016/j.bonr.2017.02.007
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365311
    Abstract
    It is generally accepted that bone and muscle possess the capacity to act in an autocrine, paracrine, or endocrine manner, with a growing body of evidence that suggests muscle can secrete muscle specific cytokines or "myokines", which influence bone metabolism. However, there has been little investigation into the identity of bone specific cytokines that modulate skeletal muscle differentiation and function. This study aimed to elucidate the influence of osteocytes on muscle progenitor cells in vitro and to identify potential bone specific cytokines or "osteokines". We treated C2C12 myoblasts with media collected from differentiated osteocytes (Ocy454 cells) grown in 3D, either under static or fluid flow culture conditions (2 dynes/cm2). C2C12 differentiation was significantly inhibited with a 75% reduction in the number of myofibers formed. mRNA analysis revealed a significant reduction in the expression of myogenic regulatory genes. Cytokine array analysis on the conditioned media demonstrated that osteocytes produce a significant number of cytokines "osteokines" capable of inhibiting myogenesis. Furthermore, we demonstrated that when osteocytes are mechanically activated they induce a greater inhibitory effect on myogenesis compared to a static state. Lastly, we identified the downregulation of numerous cytokines, including Il-6, Il-13, Il-1β, MIP-1α, and Cxcl9, involved in myogenesis, which may lead to future investigation of the role "osteokines" play in musculoskeletal health and pathology.

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