Wang Feng-Sheng, Wu Re-Wen, Chen Yu-Shan, Ko Jih-Yang, Jahr Holger, Lian Wei-Shiung
Core Laboratory for Phenomics and Diagnostic, Department of Medical Research and Chang Gung University College of Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.
Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.
Antioxidants (Basel). 2021 Aug 30;10(9):1394. doi: 10.3390/antiox10091394.
Bone-forming cells build mineralized microstructure and couple with bone-resorbing cells, harmonizing bone mineral acquisition, and remodeling to maintain bone mass homeostasis. Mitochondrial glycolysis and oxidative phosphorylation pathways together with ROS generation meet the energy requirement for bone-forming cell growth and differentiation, respectively. Moderate mechanical stimulations, such as weight loading, physical activity, ultrasound, vibration, and electromagnetic field stimulation, etc., are advantageous to bone-forming cell activity, promoting bone anabolism to compromise osteoporosis development. A plethora of molecules, including ion channels, integrins, focal adhesion kinases, and myokines, are mechanosensitive and transduce mechanical stimuli into intercellular signaling, regulating growth, mineralized extracellular matrix biosynthesis, and resorption. Mechanical stimulation changes mitochondrial respiration, biogenesis, dynamics, calcium influx, and redox, whereas mechanical disuse induces mitochondrial dysfunction and oxidative stress, which aggravates bone-forming cell apoptosis, senescence, and dysfunction. The control of the mitochondrial biogenesis activator PGC-1α by NAD+-dependent deacetylase sirtuins or myokine FNDC/irisin or repression of oxidative stress by mitochondrial antioxidant Nrf2 modulates the biophysical stimulation for the promotion of bone integrity. This review sheds light onto the roles of mechanosensitive signaling, mitochondrial dynamics, and antioxidants in mediating the anabolic effects of biophysical stimulation to bone tissue and highlights the remedial potential of mitochondrial biogenesis regulators for osteoporosis.
成骨细胞构建矿化微结构并与破骨细胞相互配合，协调骨矿物质获取和重塑过程，以维持骨量稳态。线粒体糖酵解和氧化磷酸化途径以及活性氧生成分别满足成骨细胞生长和分化的能量需求。适度的机械刺激，如负重、体育活动、超声、振动和电磁场刺激等，有利于成骨细胞活性，促进骨合成代谢以对抗骨质疏松症的发展。大量分子，包括离子通道、整合素、黏着斑激酶和肌动蛋白等，具有机械敏感性，可将机械刺激转化为细胞间信号，调节生长、矿化细胞外基质生物合成和吸收。机械刺激会改变线粒体呼吸、生物发生、动力学、钙内流和氧化还原状态，而机械失用会诱导线粒体功能障碍和氧化应激，从而加重成骨细胞凋亡、衰老和功能障碍。通过烟酰胺腺嘌呤二核苷酸（NAD+）依赖性脱乙酰酶sirtuins或肌动蛋白FNDC/鸢尾素对线粒体生物发生激活剂PGC-1α的调控，或通过线粒体抗氧化剂Nrf2对氧化应激的抑制，可调节生物物理刺激以促进骨完整性。本综述揭示了机械敏感信号、线粒体动力学和抗氧化剂在介导生物物理刺激对骨组织的合成代谢作用中的作用，并强调了线粒体生物发生调节剂对骨质疏松症的治疗潜力。
