{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:32:19Z","timestamp":1789770739337,"version":"4.0.1"},"reference-count":109,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NHRI-EX110-11029SI"],"award-info":[{"award-number":["NHRI-EX110-11029SI"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CORPG8L029"],"award-info":[{"award-number":["CORPG8L029"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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-1\u03b1 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.<\/jats:p>","DOI":"10.3390\/antiox10091394","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T11:01:37Z","timestamp":1630321297000},"page":"1394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Biophysical Modulation of the Mitochondrial Metabolism and Redox in Bone Homeostasis and Osteoporosis: How Biophysics Converts into Bioenergetics"],"prefix":"10.3390","volume":"10","author":[{"given":"Feng-Sheng","family":"Wang","sequence":"first","affiliation":[{"name":"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"},{"name":"Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3698-1704","authenticated-orcid":false,"given":"Re-Wen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Chang Gung University College of Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Shan","family":"Chen","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jih-Yang","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Chang Gung University College of Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Jahr","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University Hospital RWTH, 52074 Aachen, Germany"},{"name":"Department of Orthopedic Surgery, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Shiung","family":"Lian","sequence":"additional","affiliation":[{"name":"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"},{"name":"Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S0140-6736(18)32112-3","article-title":"Osteoporosis","volume":"393","author":"Compston","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1080\/03008207.2017.1290085","article-title":"Osteoblast-osteoclast interactions","volume":"59","author":"Chen","year":"2018","journal-title":"Connect. 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