{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:54:42Z","timestamp":1785430482827,"version":"3.56.0"},"reference-count":49,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["12374442"],"award-info":[{"award-number":["12374442"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["12374442"],"award-info":[{"award-number":["12374442"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009103","name":"Education Department of Shaanxi Province","doi-asserted-by":"publisher","award":["No. 2025JC-YBMS-046"],"award-info":[{"award-number":["No. 2025JC-YBMS-046"]}],"id":[{"id":"10.13039\/501100009103","id-type":"DOI","asserted-by":"publisher"}]},{"award":["No. 2025JC-YBMS-046"],"award-info":[{"award-number":["No. 2025JC-YBMS-046"]}],"id":[{"id":"https:\/\/ror.org\/00jb7xy46","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Osteoporosis and hyperglycemia are increasingly recognized as dual public health concerns in T1DM. However, the precise molecular mechanisms by which exercise ameliorates these conditions, particularly the contribution of mechanosensitive channels such as Piezo1, remain incompletely elucidated. To explore these mechanisms, T1DM mice were subjected to a 6-week treadmill training protocol (15 m\/min, 20 min\/day, 6 days\/week) to evaluate the functions of exercise on diabetic osteoporosis and hyperglycemia. Exercise intervention markedly improved bone quality in T1DM mice, alleviating osteoporotic manifestations, as evidenced by enhanced mechanical strength, restored bone microarchitecture, and normalized histomorphology. Concurrently, exercise significantly reduced hyperglycemia. To clarify the role of Piezo1, mechanical stretch was applied to Piezo1-knockout MC3T3-E1 (Piezo1\u2212\/\u2212) cells in vitro, mimicking the mechanical stimulation induced by exercise. Consistent with the in vivo results, mechanical stimulation facilitated osteogenic differentiation and glucose metabolism through Piezo1-mediated mechanotransduction. Importantly, these beneficial effects were substantially abrogated in Piezo1\u2212\/\u2212 cells, highlighting the central role of Piezo1. Collectively, these findings demonstrate that Piezo1-mediated mechanotransduction constitutes a critical factor by which exercise mitigates osteoporosis and hyperglycemia in T1DM mice. This study provides a framework for the development of new therapeutic strategies targeting Piezo1-mediated mechanotransduction for T1DM management.<\/jats:p>","DOI":"10.3390\/biology15110819","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:33:54Z","timestamp":1779687234000},"page":"819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exercise Alleviates Osteoporosis and Hyperglycemia in Type 1 Diabetes Mellitus Mice via Piezo1-Mediated Mechanotransduction"],"prefix":"10.3390","volume":"15","author":[{"given":"Mengshu","family":"Cao","sequence":"first","affiliation":[{"name":"Institute of Sports Biology, Physical Education School, Shaanxi Normal University, Chang\u2019an Campus, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Pang","sequence":"additional","affiliation":[{"name":"Institute of Sports Biology, Physical Education School, Shaanxi Normal University, Chang\u2019an Campus, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Sports Biology, Physical Education School, Shaanxi Normal University, Chang\u2019an Campus, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzheng","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Sports Biology, Physical Education School, Shaanxi Normal University, Chang\u2019an Campus, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sainan","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Sports Biology, Physical Education School, Shaanxi Normal University, Chang\u2019an Campus, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Sports Biology, Physical Education School, Shaanxi Normal University, Chang\u2019an Campus, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiushan","family":"Fan","sequence":"additional","affiliation":[{"name":"Institute of Sports Biology, Physical Education School, Shaanxi Normal University, Chang\u2019an Campus, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Tang","sequence":"additional","affiliation":[{"name":"Institute of Sports Biology, Physical Education School, Shaanxi Normal University, Chang\u2019an Campus, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","first-page":"17016","article-title":"Type 1 diabetes mellitus","volume":"3","author":"Katsarou","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"110980","DOI":"10.1016\/j.diabres.2023.110980","article-title":"Medications and medical expenditures for diabetic patients with osteoporosis in Beijing, China: A retrospective study","volume":"206","author":"Pan","year":"2023","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1007\/s12020-017-1286-5","article-title":"An update on the potential role of C-peptide in diabetes and osteoporosis","volume":"58","author":"Pujia","year":"2017","journal-title":"Endocrine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"102918","DOI":"10.1016\/j.dsx.2023.102918","article-title":"Self-management of type 1 diabetes in young adults: Is it impeded by aspects of everyday life? A scoping review","volume":"17","author":"Shiel","year":"2023","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1016\/S0140-6736(18)31320-5","article-title":"Type 1 diabetes","volume":"391","author":"DiMeglio","year":"2018","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/S2213-8587(17)30188-2","article-title":"Osteoporosis treatment: Recent developments and ongoing challenges","volume":"5","author":"Khosla","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/ten.teb.2015.0357","article-title":"A review of the clinical side effects of bone morphogenetic protein-2","volume":"22","author":"James","year":"2016","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s11914-016-0306-3","article-title":"Advances in nanotechnology for the treatment of osteoporosis","volume":"14","author":"Barry","year":"2016","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1089\/ten.teb.2020.0168","article-title":"Injectable hydrogels as three-dimensional network reservoirs for osteoporosis treatment","volume":"27","author":"Zheng","year":"2021","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Macias, I., Alcorta-Sevillano, N., Rodriguez, C.I., and Infante, A. (2020). Osteoporosis and the potential of cell-based therapeutic strategies. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051653"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Aibar-Almazan, A., Voltes-Martinez, A., Castellote-Caballero, Y., Afanador-Restrepo, D.F., Carcelen-Fraile, M.D.C., and Lopez-Ruiz, E. (2022). Current status of the diagnosis and management of osteoporosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169465"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11458","DOI":"10.1021\/acs.chemrev.0c01062","article-title":"Hydrogels in emerging technologies for type 1 diabetes","volume":"121","author":"Fuchs","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"115205","DOI":"10.1016\/j.addr.2024.115205","article-title":"Encapsulation and immune protection for type 1 diabetes cell therapy","volume":"207","author":"Kioulaphides","year":"2024","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/s41574-018-0117-y","article-title":"Closed-loop insulin delivery has wide-ranging benefits","volume":"14","author":"Morris","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1021\/acsbiomaterials.9b01406","article-title":"Engineering strategies to improve islet transplantation for type 1 diabetes therapy","volume":"6","author":"White","year":"2020","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/nrendo.2016.178","article-title":"Clinical pancreatic islet transplantation","volume":"13","author":"Shapiro","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Jiang, Z., Zhao, T., Ye, M., Hu, C., Yin, Z., Li, H., Zhang, Y., Diao, Y., and Li, Y. (2012). Reversal of type 1 diabetes via islet beta cell regeneration following immune modulation by cord blood-derived multipotent stem cells. BMC Med., 10.","DOI":"10.1186\/1741-7015-10-3"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1007\/s13346-022-01233-3","article-title":"Nanomaterials for antigen-specific immune tolerance therapy","volume":"13","author":"Park","year":"2023","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e2000164","DOI":"10.1002\/adhm.202000164","article-title":"Nano and microparticle emerging strategies for treatment of autoimmune diseases: Multiple sclerosis and type 1 diabetes","volume":"9","author":"Kwiatkowski","year":"2020","journal-title":"Adv. Healthc. Mater."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"212939","DOI":"10.1016\/j.bioadv.2022.212939","article-title":"Cationized silica ceria nanocomposites to target biofilms in chronic wounds","volume":"138","author":"Rasool","year":"2022","journal-title":"Biomater. Adv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8570","DOI":"10.1002\/jcp.27833","article-title":"Prospect of mesenchymal stem cells in therapy of osteoporosis: A review","volume":"234","author":"Dolati","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1177\/1932296814566231","article-title":"Physical activity and type 1 diabetes: Time for a rewire?","volume":"9","author":"Colberg","year":"2015","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1055\/s-0034-1372581","article-title":"Importance of exercise in the control of metabolic and inflammatory parameters at the moment of onset in type 1 diabetic subjects","volume":"122","author":"Alonso","year":"2014","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1080\/87559129.2021.1926483","article-title":"Protective effect of indian herbs and physical exercise on osteoporosis: A review","volume":"39","author":"Chahal","year":"2023","journal-title":"Food Rev. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4786","DOI":"10.1210\/en.2004-1653","article-title":"Estrogen and exercise may enhance \u03b2-cell function and mass via insulin receptor substrate 2 induction in ovariectomized diabetic rats","volume":"146","author":"Choi","year":"2005","journal-title":"Endocrinology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s00592-017-0978-x","article-title":"Why should people with type 1 diabetes exercise regularly?","volume":"54","author":"Codella","year":"2017","journal-title":"Acta Diabetol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41413-021-00168-8","article-title":"Roles of mechanosensitive channel Piezo1\/2 proteins in skeleton and other tissues","volume":"9","author":"Qin","year":"2021","journal-title":"Bone Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature25453","article-title":"Structure of the mechanically activated ion channel Piezo1","volume":"554","author":"Saotome","year":"2018","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2303494","DOI":"10.1002\/smll.202303494","article-title":"Bone-targeted biomimetic nanogels re-establish osteoblast\/osteoclast balance to treat postmenopausal osteoporosis","volume":"20","author":"Cui","year":"2024","journal-title":"Small"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s11658-019-0136-2","article-title":"miR-29b-3p regulated osteoblast differentiation via regulating IGF-1 secretion of mechanically stimulated osteocytes","volume":"24","author":"Zeng","year":"2019","journal-title":"Cell Mol. Biol. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"119581","DOI":"10.1016\/j.jep.2025.119581","article-title":"Network pharmacology analysis uncovers the mechanism of Shudihuang-Shanzhuyu herb pair in prevention and treatment of diabetic osteoporosis via PI3K\/AKT pathway","volume":"345","author":"Hu","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/cbf.3415","article-title":"The molecular mechanism study of insulin on proliferation and differentiation of osteoblasts under high glucose conditions","volume":"37","author":"Zhang","year":"2019","journal-title":"Cell Biochem. Funct."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4437","DOI":"10.1038\/s41467-025-59719-w","article-title":"FABP4 inhibition suppresses bone resorption and protects against postmenopausal osteoporosis in ovariectomized mice","volume":"16","author":"Xie","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.2337\/dc15-0783","article-title":"Type 1 diabetes is associated with an increased risk of fracture across the life span: A population-based cohort study using the health improvement network (THIN)","volume":"38","author":"Weber","year":"2015","journal-title":"Diabetes Care"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.2337\/dc16-1162","article-title":"A contemporary estimate of total mortality and cardiovascular disease risk in young adults with type 1 diabetes: The pittsburgh epidemiology of diabetes complications study","volume":"39","author":"Miller","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14929","DOI":"10.1038\/s41598-022-19031-9","article-title":"Changes of macrophage and CD4 T cell in inflammatory response in type 1 diabetic mice","volume":"12","author":"Li","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_37","first-page":"387","article-title":"Regulation of bone metabolism by Wnt signals","volume":"159","author":"Kobayashi","year":"2016","journal-title":"Int. J. Mol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1002\/jbmr.3812","article-title":"Expression of a degradation-resistant beta-catenin mutant in osteocytes protects the skeleton from mechanodeprivation-induced bone wasting","volume":"34","author":"Bullock","year":"2019","journal-title":"J. Bone Miner. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"245","DOI":"10.4049\/jimmunol.1103387","article-title":"Crystal structure of human RANKL complexed with its decoy receptor osteoprotegerin","volume":"189","author":"Luan","year":"2012","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1021\/acschembio.4c00382","article-title":"Facile generation of neutralizing antibodies on tyrosine phosphorylated irs1 by epitope-directed elicitation","volume":"19","author":"Xiang","year":"2024","journal-title":"ACS Chem. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.cell.2007.05.047","article-title":"Endocrine regulation of energy metabolism by the skeleton","volume":"130","author":"Lee","year":"2007","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"830","DOI":"10.2337\/dc21-2113","article-title":"Osteocalcin and risks of incident diabetes and diabetic kidney disease: A 4.6-year prospective cohort study","volume":"45","author":"Ye","year":"2022","journal-title":"Diabetes Care"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.4239\/wjd.v6.i18.1345","article-title":"Osteocalcin as a hormone regulating glucose metabolism","volume":"6","author":"Kanazawa","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Xu, X., Liu, S.Y., Liu, H., Ru, K., Jia, Y.X., Wu, Z.X., Liang, S.J., Khan, Z., Chen, Z.H., and Qian, A.R. (2021). Piezo channels: Awesome mechanosensitive structures in cellular mechanotransduction and their role in bone. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126429"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nature21407","article-title":"Mechanical stretch triggers rapid epithelial cell division through Piezo1","volume":"543","author":"Gudipaty","year":"2017","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1126\/science.1193270","article-title":"Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels","volume":"330","author":"Coste","year":"2010","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1136\/ard-2022-223428","article-title":"Piezo1-mediated mechanotransduction promotes entheseal pathological new bone formation in ankylosing spondylitis","volume":"82","author":"Chen","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e47454","DOI":"10.7554\/eLife.47454","article-title":"The mechanosensitive Piezo1 channel is required for bone formation","volume":"8","author":"Sun","year":"2019","journal-title":"Elife"},{"key":"ref_49","first-page":"13","article-title":"Targeting the central and peripheral nervous system to regulate bone homeostasis: Mechanisms and potential therapies","volume":"12","author":"Liang","year":"2025","journal-title":"Mil. Med. Res."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/11\/819\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T04:10:41Z","timestamp":1779768641000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/11\/819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":49,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["biology15110819"],"URL":"https:\/\/doi.org\/10.3390\/biology15110819","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]}}}