Osteocalcin inhibits myocyte aging through promotion of starvation-induced autophagy via IL-6/STAT3 signaling
This study aimed to investigate the effects and mechanisms of osteocalcin on autophagy in myoblasts, as well as its possible therapeutic effects in aging muscle. Starved murine myoblast C2C12 cells with or without interleukin (IL)-6 siRNA were treated with osteocalcin. Expression of the autophagy pr...
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Published in | Experimental gerontology Vol. 173; p. 112082 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Elsevier Inc
01.03.2023
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | This study aimed to investigate the effects and mechanisms of osteocalcin on autophagy in myoblasts, as well as its possible therapeutic effects in aging muscle. Starved murine myoblast C2C12 cells with or without interleukin (IL)-6 siRNA were treated with osteocalcin. Expression of the autophagy protein marker LC3, as well as IL-6 and phosphorylated STAT3 were detected by immunoblotting, immunofluorescence, or immunohistochemistry. Autophagosomes were observed with transmission electron microscopy. Levels of reactive oxygen species (ROS) were detected by flow cytometry. Fasted young mice were injected intraperitoneally with osteocalcin, with or without the JAK inhibitor CP-690550 to inhibit IL-6 signaling. Older mice were treated with osteocalcin and muscle mass, grip strength and muscle structure were assessed. The results revealed that compared to control and serum-starved cells, osteocalcin treatment significantly increased the relative expression of LC3-II/LC3-I protein, the numbers of autophagosomes, and levels of intracellular ROS. Osteocalcin injection in mice also resulted in increased relative LC3-II/LC3-I protein expression and autophagosome numbers. Osteocalcin treatment significantly increased the secretion of IL-6 in muscle cells and tissue, and activated STAT3 signaling. Moreover, knockdown of IL-6 or blocking IL-6 signaling inhibited the phosphorylation of STAT3, and further inhibited autophagy in starved myoblasts and fasting-treated murine muscle tissue. In addition, osteocalcin treatment significantly increased muscle mass and grip strength in both aged mice and aged fasting mice. In conclusion, the inhibition of osteocalcin on muscle cell aging is accompanied by the induction of IL-6-STAT3-dependent autophagy, indicating osteocalcin might be a promising therapeutic candidate for aging-related myopathies.
•Osteocalcin promotes starvation or fasting-induced myocyte autophagy.•Osteocalcin increases the secretion of IL-6 and phosphorylation of STAT3.•Osteocalcin alleviates muscle aging in aged mice via IL-6/STAT3 signaling. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0531-5565 1873-6815 |
DOI: | 10.1016/j.exger.2023.112082 |