Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise

Mera, Paula; Laue, Kathrin; Ferron, Mathieu; Confavreux, C; Wei, Jianwen; Galán-Díez, Marta; Lacampagne, Alain; Mitchell, Sarah J.; Mattison, Julie A.; Chen, Yun; Bacchetta, Justine; Szulc, Paweł; Kitsis, Richard N.; Cabo, Rafael de; Friedman, Richard A.; Torsitano, Christopher; McGraw, Timothy E.; Puchowicz, Michelle; Kurland, Irwin J.; Karsenty, G.

doi:10.1016/j.cmet.2016.12.003

Cited by 42 publications

(52 citation statements)

References 29 publications

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“…In addition, osteocalcin supplementation raised the exercise capacity in young mice and reversed the age‐related decline in aerobic endurance. Osteocalcin signaling in myofibers is also the main reason for the aerobic exercise‐induced release of myokine IL‐6 . Interestingly, chronic delivery of osteocalcin not only increases muscle function but also improves muscle mass in older mice .…”

Section: Muscle‐bone Biochemical Crosstalk and Solute Factorsmentioning

confidence: 99%

“…Osteocalcin signaling in myofibers is also the main reason for the aerobic exercise‐induced release of myokine IL‐6 . Interestingly, chronic delivery of osteocalcin not only increases muscle function but also improves muscle mass in older mice . Another evidence for the effects of osteocalcin on muscle is that muscle phenotypes (i.e., muscle mass, grip strength, fiber numbers, myosin heavy chain isoforms, and maximum contraction force) were altered in mice with osteoblast/osteocyte specific deletion of Cx43 gene ( Gja1 ) .…”

Section: Muscle‐bone Biochemical Crosstalk and Solute Factorsmentioning

confidence: 99%

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Muscle‐bone crosstalk and potential therapies for sarco‐osteoporosis

Zhang

Wang

et al. 2019

J of Cellular Biochemistry

104

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The nature of muscle‐bone crosstalk has been historically considered to be only mechanical, where the muscle is the load applier while bone provides the attachment sites. However, this dogma has been challenged with the emerging notion that bone and muscle act as secretory endocrine organs affect the function of each other. Biochemical crosstalk occurs through myokines such as myostatin, irisin, interleukin (IL)‐6, IL‐7, IL‐15, insulin‐like growth factor‐1, fibroblast growth factor (FGF)‐2, and β‐aminoisobutyric acid and through bone‐derived factors including FGF23, prostaglandin E2, transforming growth factor β, osteocalcin, and sclerostin. Aside from the biochemical and mechanical interaction, additional factors including aging, circadian rhythm, nervous system network, nutrition intake, and exosomes also have effects on bone‐muscle crosstalk. Here, we summarize the current research progress in the area, which may be conductive to identify potential novel therapies for the osteoporosis and sarcopenia, especially when they develop in parallel.

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Section: Muscle‐bone Biochemical Crosstalk and Solute Factorsmentioning

confidence: 99%

Section: Muscle‐bone Biochemical Crosstalk and Solute Factorsmentioning

confidence: 99%

Muscle‐bone crosstalk and potential therapies for sarco‐osteoporosis

Zhang

Wang

et al. 2019

J of Cellular Biochemistry

104

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“…AMPK plays an important role in muscle energy metabolism . It is possible that ucOC activates AMPK signaling in skeletal muscle, thereby contributing to the beneficial effects of ucOC on glucose uptake . However, we and others have reported an unlikely role of AMPKα Thr172 phosphorylation in the ucOC effects in C2C12 myotubes, ex vivo mouse muscle, and human muscle .…”

Section: Discussionmentioning

confidence: 58%

“…GPRC6A is the putative receptor for ucOC in muscle cells . The ucOC effect on muscle cells appears to involve the enhancement of GPRC6A expression .…”

Section: Discussionmentioning

confidence: 99%

Undercarboxylated Osteocalcin Improves Insulin-Stimulated Glucose Uptake in Muscles of Corticosterone-Treated Mice

Lin

Parker

McLennan

et al. 2019

Journal of Bone and Mineral Research

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Short‐term administration of glucocorticoids (GCs) impairs muscle insulin sensitivity at least in part via the reduction of undercarboxylated osteocalcin (ucOC). However, whether ucOC treatment reverses the GC‐induced muscle insulin resistance remains unclear. To test the hypothesis that ucOC directly ameliorates impaired insulin‐stimulated glucose uptake (ISGU) induced by short‐term GC administration in mice muscle and to identify the molecular mechanisms, mice were implanted with placebo or corticosterone (CS) slow‐release pellets. Two days post‐surgery, insulin‐tolerance tests (ITTs) were performed. On day 3, serum was collected and extensor digitorum longus (EDL) and soleus muscles were isolated and treated ex vivo with vehicle, ucOC (30 ng/mL), insulin (60 µU/mL), or both. Circulating hormone levels, muscle glucose uptake, and muscle signaling proteins were assessed. CS administration reduced both serum osteocalcin and ucOC levels, whole‐body insulin sensitivity, and muscle ISGU in EDL. Ex vivo ucOC treatment restored ISGU in CS‐affected muscle, without increasing non‐insulin‐stimulated glucose uptake. In CS‐affected EDL muscle, ucOC enhanced insulin action on phosphorylated (p‐)protein kinase B (Akt)Ser473and the p‐extracellular signal‐regulated kinase isoform 2 (ERK2)Thr202/Tyr204/total (t)ERK2 ratio, which correlated with ISGU. In CS‐affected soleus muscle, ucOC enhanced insulin action on p‐mammalian target of rapamycin (mTOR)Ser2481, the p‐mTORSer2481/tmTOR ratio, p‐Akt substrate of 160kD (AS160)Thr642, and p‐protein kinase C (PKC) (pan)Thr410, which correlated with ISGU. Furthermore, p‐PKC (pan)Thr410 correlated with p‐AktSer473 and p‐AS160Thr642. ucOC exerts direct insulin‐sensitizing effects on CS‐affected mouse muscle, likely through an enhancement in activity of key proteins involved in both insulin and ucOC signaling pathways. Furthermore, these effects are muscle type‐dependent. © 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.

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“…Indeed, the age‐associated reduction in osteocalcin results in elevated anxiety‐like behavior in mice as well as deficiencies in memory and learning . Bone‐derived osteocalcin also has a role in skeletal muscle where it increases IL‐6 production as well as glucose uptake and catabolism for energy production to promote adaptation to exercise . Because the functions of osteocalcin decline in mice with aging, this hormone represents another example of age‐related changes in one tissue (ie, bone) that can lead to altered intercellular communication and deterioration in multiple other tissues.…”

Section: Altered Intercellular Communicationmentioning

confidence: 99%

The Spectrum of Fundamental Basic Science Discoveries Contributing to Organismal Aging

Farr

Almeida

2018

Journal of Bone and Mineral Research

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Aging research has undergone unprecedented advances at an accelerating rate in recent years, leading to excitement in the field as well as opportunities for imagination and innovation. Novel insights indicate that, rather than resulting from a preprogrammed series of events, the aging process is predominantly driven by fundamental non-adaptive mechanisms that are interconnected, linked, and overlap. To varying degrees, these mechanisms also manifest with aging in bone where they cause skeletal fragility. Because these mechanisms of aging can be manipulated, it might be possible to slow, delay, or alleviate multiple age-related diseases and their complications by targeting conserved genetic signaling pathways, controlled functional networks, and basic biochemical processes. Indeed, findings in various mammalian species suggest that targeting fundamental aging mechanisms (eg, via either loss-of-function or gain-of-function mutations or administration of pharmacological therapies) can extend healthspan; ie, the healthy period of life free of chronic diseases. In this review, we summarize the evidence supporting the role of the spectrum of fundamental basic science discoveries contributing to organismal aging, with emphasis on mammalian studies and in particular aging mechanisms in bone that drive skeletal fragility. These mechanisms or aging hallmarks include: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Because these mechanisms are linked, interventions that ameliorate one hallmark can in theory ameliorate others. In the field of bone and mineral research, current challenges include defining the relative contributions of each aging hallmark to the natural skeletal aging process, better understanding the complex interconnections among the hallmarks, and identifying the most effective therapeutic strategies to safely target multiple hallmarks. Based on their interconnections, it may be feasible to simultaneously interfere with several fundamental aging mechanisms to alleviate a wide spectrum of age-related chronic diseases, including osteoporosis. © 2018 American Society for Bone and Mineral Research.

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Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise

Cited by 42 publications

References 29 publications

Muscle‐bone crosstalk and potential therapies for sarco‐osteoporosis

Muscle‐bone crosstalk and potential therapies for sarco‐osteoporosis

Undercarboxylated Osteocalcin Improves Insulin-Stimulated Glucose Uptake in Muscles of Corticosterone-Treated Mice

The Spectrum of Fundamental Basic Science Discoveries Contributing to Organismal Aging

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