Osteocyte secreted factors inhibit skeletal muscle differentiation
Open accessAbstract
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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These effects suggest a regulatory loop involving osteocytes and muscle metabolism, particularly since osteocytes inhibit skeletal muscle differentiation by producing a large number of cytokines, which might permeate the periosteum or diffuse into the circulation to negatively regulate myogenesis.
“These effects suggest a regulatory loop involving osteocytes and muscle metabolism, particularly since osteocytes inhibit skeletal muscle differentiation by producing a large number of cytokines, which might permeate the periosteum or diffuse into the circulation to negatively regulate myogenesis109.”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [109]
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- Authors
- Wood, C. L., Pajevic, P. D., & Gooi, J. H.
- Affiliations
- The University of Melbourne (AU)
- Boston University (US)
- Corresponding author
- Gooi, Jonathan H.
- Venue
- Bone Reports
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 6
- Pages
- 74-80
- ISSN
- 2352-1872 (ISSN-L)
- PMC
- PMC5365311
- OpenAlex
- W2594038089
- Cited by
- 24
- References
- 32
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 7 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 2
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Bone Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- osteocytes, osteokines, skeletal muscle differentiation, C2C12 myoblasts, mechanical loading, interleukin-6, IL-13, IL-1β, MIP-1α, CXCL9, muscle-bone crosstalk
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