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运动诱导的小鼠骨骼肌和骨骼之间的相互作用:FNDC5/鸢尾素、IGF-1 和骨钙素的作用。

Exercise-induced interactions between skeletal muscle and bone via myokines and osteokine in mice: Role of FNDC5/irisin, IGF-1, and osteocalcin.

机构信息

Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Kobe, Japan.

Life and Medical Sciences Area, Health Sciences Discipline, Kobe University, Kobe, Japan.

出版信息

Bone. 2025 Jan;190:117314. doi: 10.1016/j.bone.2024.117314. Epub 2024 Oct 31.

DOI:10.1016/j.bone.2024.117314
PMID:39486601
Abstract

Skeletal muscle and bone interact to maintain their structure and function. Physical exercise is the most effective and easily applicable strategy to maintain their functions; however, exercise-induced interactions by soluble factors remained elusive. Our study aimed to identify exercise-induced interactions between muscle and bone by examining (1) the effects of myokine on bone and (2) the effects of osteocalcin (OCN) on skeletal muscle. To understand the effects of exercise-induced myokines on bone, we examined the effects of FNDC5 for aerobic exercise and IGF-1 for resistance exercise using a muscle-specific myokine overexpression model. To examine OCN effects on muscle, mice were intraperitoneally administered OCN-neutralizing antibody during long-term exercise. Our result showed that aerobic exercise tended to increase serum HA-tag protein attached to FNDC5 in muscle-specific overexpression groups. In addition, osteoblastic activation was increased only after aerobic exercise with HA/FNDC5 overexpression. Resistance exercise did not alter circulating HA-tag (muscle-derived IGF-1) and bone metabolism after IGF-1/HA overexpression. In the OCN study, aerobic exercise enhanced endurance capacity by restoring muscle glycogen content; however, OCN neutralization returned these to baseline. After resistance exercise, OCN suppression inhibited muscle hypertrophy and strength gains by preventing protein synthesis. Our results suggest that aerobic exercise following FNDC5 muscle overexpression promotes osteoblast activity, which may be partially caused by muscle-derived FNDC5 secretion. In addition, OCN was necessary for muscle adaptation in both aerobic and resistance exercises.

摘要

骨骼肌和骨骼相互作用以维持其结构和功能。体育锻炼是维持其功能最有效和易于应用的策略;然而,运动诱导的可溶性因子相互作用仍然难以捉摸。我们的研究旨在通过检查(1)肌因子对骨骼的影响和(2)骨钙素(OCN)对骨骼肌的影响,来确定运动诱导的肌肉和骨骼之间的相互作用。为了了解运动诱导的肌因子对骨骼的影响,我们使用肌肉特异性肌因子过表达模型检查了 FNDC5 对有氧运动和 IGF-1 对抗阻运动的影响。为了研究 OCN 对肌肉的影响,我们在长期运动期间向小鼠腹腔内给予 OCN 中和抗体。我们的结果表明,有氧运动倾向于增加肌肉特异性过表达组中 HA 标记蛋白与 FNDC5 的结合。此外,只有在有氧锻炼与 HA/FNDC5 过表达后,成骨细胞的激活才会增加。IGF-1/HA 过表达后,抗阻运动不会改变循环 HA 标记(肌肉源性 IGF-1)和骨代谢。在 OCN 研究中,有氧运动通过恢复肌肉糖原含量来增强耐力能力;然而,OCN 中和将这些恢复到基线。在抗阻运动后,OCN 抑制通过阻止蛋白质合成抑制肌肉肥大和力量增加。我们的结果表明,FNDC5 肌肉过表达后的有氧运动促进成骨细胞活性,这可能部分是由肌肉源性 FNDC5 分泌引起的。此外,OCN 是有氧和抗阻运动中肌肉适应所必需的。

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