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Osteocalcin is necessary and sufficient to maintain muscle mass in older mice
Open accessAbstract
OBJECTIVE: A decrease in muscle protein turnover and therefore in muscle mass is a hallmark of aging. Because the circulating levels of the bone-derived hormone osteocalcin decline steeply during aging in mice, monkeys and humans we asked here whether this hormone might regulate muscle mass as mice age. METHODS: We examined muscle mass and strength in mice lacking osteocalcin (Ocn-/-) or its receptor in all cells (Gprc6a-/-) or specifically in myofibers (Gprc6a Mck -/-) as well as in 9 month-old WT mice receiving exogenous osteocalcin for 28 days. We also examined protein synthesis in WT and Gprc6a-/- mouse myotubes treated with osteocalcin. RESULTS: We show that osteocalcin signaling in myofibers is necessary to maintain muscle mass in older mice in part because it promotes protein synthesis in myotubes without affecting protein breakdown. We further show that treatment with exogenous osteocalcin for 28 days is sufficient to increase muscle mass of 9-month-old WT mice. CONCLUSION: This study uncovers that osteocalcin is necessary and sufficient to prevent age-related muscle loss in mice.
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“Osteokines, novel exercise-inducible soluble factors secreted by osteocytes, osteo blasts, and osteoclasts, play an important role in the body’s response to exercise, mainly including RANKL [127], sclerostin [128], osteocalcin [129], fibroblast growth factor 23 (FGF23) [95], Wnt3a [130], TGF-β [131], IGF-1 [132], and prostaglandin E2 (PGE2) [133] (Figure 3).”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [129]
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“In older mice, osteocalcin signaling in the myotubes promotes protein synthesis without affecting protein breakdown via activation of the mTOR pathway, uncovering that osteocalcin is both necessary and sufficient to attenuate age-related muscle loss [129].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [129]
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Metadata
- Authors
- Mera, P., Laue, K., Wei, J., Berger, J. M., & Karsenty, G.
- Affiliations
- Columbia University Irving Medical Center (US)
- Venue
- Molecular Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 5
- Issue
- 10
- Pages
- 1042-1047
- ISSN
- 2212-8778 (ISSN-L)
- PMC
- PMC5034485
- OpenAlex
- W2479847107
- Cited by
- 223
- References
- 30
- Citations by year
- 2026: 10 · 2025: 22 · 2024: 22 · 2023: 30 · 2022: 14 · 2021: 32 · 2020: 33 · 2019: 26 · 2018: 15 · 2017: 17 · 2016: 1
- FWCI
- 10.22
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-08-01)
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Metabolism (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NIH (5RO1AR045548, PO1AG032959)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Keywords
- osteocalcin, muscle mass, muscle atrophy, aging, GPRC6A, muscle fibers, muscle protein synthesis, muscle protein turnover, muscle strength, muscle-bone crosstalk
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