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Osteocyte secreted factors inhibit skeletal muscle differentiation
Charles L Wood1, Paola Divieti Pajevic2, Jonathan H Gooi1
1Department of Medicine, St. Vincent's Hospital Melbourne, The University of Melbourne, Melbourne, VIC 3065, Australia.
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.
Insights
Bone cells called osteocytes secrete "osteokines" that inhibit muscle growth. Mechanical stress on bone cells enhances this muscle-inhibiting effect, impacting musculoskeletal health.
Area of Science:
- Biochemistry
- Cell Biology
- Musculoskeletal Science
Background:
- Bone and muscle communicate bidirectionally via secreted factors.
- While muscle-derived myokines are well-studied, bone-derived osteokines influencing muscle are less understood.
Purpose of the Study:
- To investigate the effect of osteocytes on muscle progenitor cells.
- To identify potential osteokines that regulate skeletal muscle differentiation and function.
Main Methods:
- Osteocyte-conditioned media (from static or fluid flow cultures) was used to treat C2C12 myoblasts.
- Assessed C2C12 differentiation, myogenesis markers, and cytokine profiles via mRNA and cytokine array analysis.
Main Results:
- Osteocyte media significantly inhibited C2C12 myoblast differentiation and myofiber formation.
- Mechanically activated osteocytes exhibited a stronger inhibitory effect on myogenesis.
- Identified downregulation of key myogenic regulatory genes and specific cytokines (e.g., Il-6, Il-1β) in response to osteocyte media.
Conclusions:
- Osteocytes produce osteokines that inhibit muscle progenitor cell differentiation.
- Mechanical loading of bone can potentiate the muscle-inhibiting effects of osteocytes.
- These findings suggest a novel pathway for osteokine-mediated regulation of musculoskeletal health and disease.