Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.
Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.
Biochem Biophys Res Commun. 2019 Oct 1;517(4):749-754. doi: 10.1016/j.bbrc.2019.07.127. Epub 2019 Aug 5.
Recently, muscle has received much attention as an endocrine organ regulating other biological targets, including the pancreas, liver, and adipose tissue. Although there is a possibility that muscle-secreting factors biochemically affect bone metabolism in a paracrine manner, the net effects of myokines on the biology of osteoclasts and osteoblasts, particularly on bone mass in vivo, have not yet been thoroughly investigated. Therefore, we performed in vitro as well as animal experiments using conditioned media (CM) collected from C2C12 myoblast and myotube cultures to better understand the interactions between muscle and bone. Compared with non-CM (i.e., control) and myoblast CM, myotube CM markedly inhibited in vitro bone resorption through the suppression of osteoclast differentiation and resorptive activity of individual osteoclasts. Consistently, the expressions of osteoclast differentiation markers, such as tartrate-resistant acid phosphatase (Trap) and calcitonin receptor (Ctr), decreased with myotube CM. Myotube CM significantly stimulated preosteoblast viability and migration and reduced apoptosis, thereby resulting in an increase in calvaria bone formation. Importantly, systemic treatment with myotube CM for 4 weeks increased bone per tissue volume by 30.7% and 19.6% compared with control and myoblast CM, respectively. These results support the hypothesis that muscle plays beneficial roles in bone health via secretion of anabolic factors, in addition to mechanical stimuli, and importantly indicate that muscle-derived factors can be potential therapeutic targets against metabolic bone diseases.
最近，肌肉作为一种内分泌器官受到了广泛关注，它可以调节其他生物靶标，包括胰腺、肝脏和脂肪组织。虽然肌肉分泌的因子可能通过旁分泌的方式对骨代谢产生生化影响，但是肌因子对破骨细胞和成骨细胞的生物学作用，特别是对体内骨量的影响，尚未得到彻底研究。因此，我们通过从小鼠 C2C12 成肌细胞和肌管培养物中收集条件培养基（CM）进行体外和动物实验，以更好地了解肌肉和骨骼之间的相互作用。与非 CM（即对照）和成肌细胞 CM 相比，肌管 CM 通过抑制破骨细胞分化和单个破骨细胞的吸收活性，显著抑制体外骨吸收。一致地，破骨细胞分化标志物如抗酒石酸酸性磷酸酶（Trap）和降钙素受体（Ctr）的表达随着肌管 CM 的减少而降低。肌管 CM 显著刺激前成骨细胞的活力和迁移，减少细胞凋亡，从而增加颅骨骨形成。重要的是，与对照和成肌细胞 CM 相比，用肌管 CM 进行 4 周的全身治疗分别使组织体积内的骨量增加了 30.7%和 19.6%。这些结果支持了肌肉通过分泌合成代谢因子而不仅仅是机械刺激对骨骼健康发挥有益作用的假说，并且重要的是表明肌肉来源的因子可以成为代谢性骨疾病的潜在治疗靶点。
