{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:06:55Z","timestamp":1793203615879,"version":"4.5.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:00:00Z","timestamp":1768003200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Guangdong Medical Science and Technology Research Foundation","award":["A2023145"],"award-info":[{"award-number":["A2023145"]}]},{"name":"Guangdong Provincial Sports Bureau Scientific Research Project","award":["GDSS2024N007"],"award-info":[{"award-number":["GDSS2024N007"]}]},{"name":"NSFC grant","award":["82371692, 32170825"],"award-info":[{"award-number":["82371692, 32170825"]}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"crossref","award":["021A1515012393"],"award-info":[{"award-number":["021A1515012393"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-35708-x","type":"journal-article","created":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T06:45:42Z","timestamp":1768027542000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Repurposing metformin for treating osteoarthritis via leveraging Nrf2 signaling"],"prefix":"10.1038","volume":"16","author":[{"given":"Yeyin","family":"Zhong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieying","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,10]]},"reference":[{"key":"35708_CR1","doi-asserted-by":"publisher","first-page":"9177","DOI":"10.12659\/MSM.913726","volume":"24","author":"G Gao","year":"2018","unstructured":"Gao, G. et al. Effects of hesperidin on H\u2082O\u2082-Treated chondrocytes and cartilage in a rat osteoarthritis model. Med. Sci. Monit. 24, 9177\u20139186 (2018).","journal-title":"Med. Sci. Monit."},{"issue":"10","key":"35708_CR2","doi-asserted-by":"publisher","first-page":"e3081","DOI":"10.1038\/cddis.2017.453","volume":"8","author":"Q Tang","year":"2017","unstructured":"Tang, Q. et al. Trehalose ameliorates oxidative stress-mediated mitochondrial dysfunction and ER stress via selective autophagy stimulation and autophagic flux restoration in osteoarthritis development. Cell. Death Dis. 8 (10), e3081 (2017).","journal-title":"Cell. Death Dis."},{"issue":"4","key":"35708_CR3","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.berh.2008.07.002","volume":"22","author":"SK Das","year":"2008","unstructured":"Das, S. K. & Farooqi, A. Osteoarthritis Best Pract. Res. Clin. Rheumatol., 22(4): 657\u2013675. (2008).","journal-title":"Osteoarthritis Best Pract. Res. Clin. Rheumatol."},{"issue":"6","key":"35708_CR4","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1001\/jama.2020.22171","volume":"325","author":"JN Katz","year":"2021","unstructured":"Katz, J. N., Arant, K. R. & Loeser, R. F. Diagnosis and treatment of hip and knee osteoarthritis: A review. Jama 325 (6), 568\u2013578 (2021).","journal-title":"Jama"},{"key":"35708_CR5","doi-asserted-by":"publisher","first-page":"110452","DOI":"10.1016\/j.biopha.2020.110452","volume":"129","author":"MY Ansari","year":"2020","unstructured":"Ansari, M. Y., Ahmad, N. & Haqqi, T. M. Oxidative stress and inflammation in osteoarthritis pathogenesis: role of polyphenols. Biomed. Pharmacother. 129, 110452 (2020).","journal-title":"Biomed. Pharmacother"},{"key":"35708_CR6","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1093\/bmb\/lds038","volume":"105","author":"A Litwic","year":"2013","unstructured":"Litwic, A. et al. Epidemiology and burden of osteoarthritis. Br. Med. Bull. 105, 185\u2013199 (2013).","journal-title":"Br. Med. Bull."},{"issue":"6","key":"35708_CR7","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.berh.2011.11.008","volume":"25","author":"DJ Hunter","year":"2011","unstructured":"Hunter, D. J. Osteoarthritis Best Pract. Res. Clin. Rheumatol., 25(6): 801\u2013814. (2011).","journal-title":"Osteoarthritis Best Pract. Res. Clin. Rheumatol."},{"key":"35708_CR8","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.freeradbiomed.2018.08.038","volume":"132","author":"JA Bolduc","year":"2019","unstructured":"Bolduc, J. A., Collins, J. A. & Loeser, R. F. Reactive oxygen species, aging and articular cartilage homeostasis. Free Radic Biol. Med. 132, 73\u201382 (2019).","journal-title":"Free Radic Biol. Med."},{"key":"35708_CR9","doi-asserted-by":"crossref","unstructured":"Tudorachi, N. B. et al. The implication of reactive oxygen species and antioxidants in knee osteoarthritis. Antioxid. (Basel), 10 (6), 985 (2021).","DOI":"10.3390\/antiox10060985"},{"issue":"6","key":"35708_CR10","doi-asserted-by":"publisher","first-page":"4395","DOI":"10.1111\/jcmm.14333","volume":"23","author":"F Zhou","year":"2019","unstructured":"Zhou, F. et al. Isorhamnetin attenuates osteoarthritis by inhibiting osteoclastogenesis and protecting chondrocytes through modulating reactive oxygen species homeostasis. J. Cell. Mol. Med. 23 (6), 4395\u20134407 (2019).","journal-title":"J. Cell. Mol. Med."},{"key":"35708_CR11","doi-asserted-by":"publisher","first-page":"1027553","DOI":"10.3389\/fphar.2022.1027553","volume":"13","author":"T Ma","year":"2022","unstructured":"Ma, T. et al. Ginkgolide C slows the progression of osteoarthritis by activating Nrf2\/HO-1 and blocking the NF-\u03baB pathway. Front. Pharmacol. 13, 1027553 (2022).","journal-title":"Front. Pharmacol."},{"key":"35708_CR12","doi-asserted-by":"crossref","unstructured":"He, F., Ru, X. & Wen, T. NRF2, a transcription factor for stress response and beyond. Int. J. Mol. Sci., 21 (13), 4777 (2020).","DOI":"10.3390\/ijms21134777"},{"key":"35708_CR13","doi-asserted-by":"crossref","unstructured":"Zhang et al. Four-Octyl Itaconate Protects Chondrocytes against H(2)O(2)-Induced Oxidative Injury and Attenuates Osteoarthritis Progression by Activating Nrf2 Signaling. Oxid Med Cell Longev, 2022, 2206167. (2022).","DOI":"10.1155\/2022\/2206167"},{"key":"35708_CR14","doi-asserted-by":"publisher","first-page":"1188215","DOI":"10.3389\/fphar.2023.1188215","volume":"14","author":"Z Wu","year":"2023","unstructured":"Wu, Z. et al. Natural compounds protect against the pathogenesis of osteoarthritis by mediating the NRF2\/ARE signaling. Front. Pharmacol. 14, 1188215 (2023).","journal-title":"Front. Pharmacol."},{"key":"35708_CR15","doi-asserted-by":"crossref","unstructured":"Cao, F. et al. Metformin reverses oxidative stress\u2013induced mitochondrial dysfunction in pre\u2013osteoblasts via the EGFR\/GSK\u20133\u03b2\/calcium pathway. Int. J. Mol. Med., 51 (4), 36 (2023).","DOI":"10.3892\/ijmm.2023.5239"},{"issue":"3","key":"35708_CR16","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1002\/dmrr.794","volume":"24","author":"G Formoso","year":"2008","unstructured":"Formoso, G. et al. Decreased in vivo oxidative stress and decreased platelet activation following Metformin treatment in newly diagnosed type 2 diabetic subjects. Diabetes Metab. Res. Rev. 24 (3), 231\u2013237 (2008).","journal-title":"Diabetes Metab. Res. Rev."},{"issue":"5","key":"35708_CR17","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1016\/j.dsx.2020.07.036","volume":"14","author":"KA Adeshara","year":"2020","unstructured":"Adeshara, K. A. et al. Action of Metformin therapy against advanced glycation, oxidative stress and inflammation in type 2 diabetes patients: 3 months follow-up study. Diabetes Metab. Syndr. 14 (5), 1449\u20131458 (2020).","journal-title":"Diabetes Metab. Syndr."},{"issue":"17","key":"35708_CR18","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1089\/ars.2017.7409","volume":"28","author":"N Diaz-Morales","year":"2018","unstructured":"Diaz-Morales, N. et al. Does Metformin modulate Endoplasmic reticulum stress and autophagy in type 2 diabetic peripheral blood mononuclear cells? Antioxid. Redox Signal. 28 (17), 1562\u20131569 (2018).","journal-title":"Antioxid. Redox Signal."},{"issue":"1","key":"35708_CR19","doi-asserted-by":"publisher","first-page":"16033","DOI":"10.1038\/s41598-019-52263-w","volume":"9","author":"I Pradas","year":"2019","unstructured":"Pradas, I. et al. Metformin induces lipid changes on sphingolipid species and oxidized lipids in polycystic ovary syndrome women. Sci. Rep. 9 (1), 16033 (2019).","journal-title":"Sci. Rep."},{"issue":"41","key":"35708_CR20","doi-asserted-by":"publisher","first-page":"3409","DOI":"10.1093\/eurheartj\/ehz203","volume":"40","author":"M Mohan","year":"2019","unstructured":"Mohan, M. et al. A randomized controlled trial of Metformin on left ventricular hypertrophy in patients with coronary artery disease without diabetes: the MET-REMODEL trial. Eur. Heart J. 40 (41), 3409\u20133417 (2019).","journal-title":"Eur. Heart J."},{"issue":"12","key":"35708_CR21","doi-asserted-by":"publisher","first-page":"e0261127","DOI":"10.1371\/journal.pone.0261127","volume":"16","author":"H Guo","year":"2021","unstructured":"Guo, H. et al. Metformin attenuates osteoclast-mediated abnormal subchondral bone remodeling and alleviates osteoarthritis via AMPK\/NF-\u03baB\/ERK signaling pathway. PLoS One. 16 (12), e0261127 (2021).","journal-title":"PLoS One"},{"issue":"1","key":"35708_CR22","doi-asserted-by":"publisher","first-page":"127","DOI":"10.4049\/jimmunol.1800006","volume":"203","author":"MJ Park","year":"2019","unstructured":"Park, M. J. et al. Metformin augments Anti-Inflammatory and chondroprotective properties of mesenchymal stem cells in experimental osteoarthritis. J. Immunol. 203 (1), 127\u2013136 (2019).","journal-title":"J. Immunol."},{"key":"35708_CR23","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.3389\/fphar.2020.01114","volume":"11","author":"C Wang","year":"2020","unstructured":"Wang, C. et al. Metformin mitigates cartilage degradation by activating AMPK\/SIRT1-Mediated autophagy in a mouse osteoarthritis model. Front. Pharmacol. 11, 1114 (2020).","journal-title":"Front. Pharmacol."},{"issue":"1","key":"35708_CR24","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1186\/s13018-023-03571-5","volume":"18","author":"S Yan","year":"2023","unstructured":"Yan, S. et al. Metformin regulates chondrocyte senescence and proliferation through microRNA-34a\/SIRT1 pathway in osteoarthritis. J. Orthop. Surg. Res. 18 (1), 198 (2023).","journal-title":"J. Orthop. Surg. Res."},{"key":"35708_CR25","doi-asserted-by":"crossref","unstructured":"Pitcher, T., Sousa-Valente, J. & Malcangio, M. The monoiodoacetate model of osteoarthritis pain in the mouse. J. Vis. Exp., 111, e53746 (2016).","DOI":"10.3791\/53746"},{"issue":"2","key":"35708_CR26","first-page":"176","volume":"52","author":"WA Hill","year":"2013","unstructured":"Hill, W. A. et al. Repeated administration of tribromoethanol in C57BL\/6NHsd mice. J. Am. Assoc. Lab. Anim. Sci. 52 (2), 176\u2013179 (2013).","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"35708_CR27","unstructured":"Association, A. V. M. AVMA Guidelines for the Euthanasia of Animals: 2020 Edition (American Veterinary Medical Association: Schaumburg, IL, 2020)."},{"issue":"7","key":"35708_CR28","doi-asserted-by":"publisher","first-page":"e3000411","DOI":"10.1371\/journal.pbio.3000411","volume":"18","author":"N Percie du Sert","year":"2020","unstructured":"Percie du Sert, N. et al. Reporting animal research: explanation and elaboration for the ARRIVE guidelines 2.0. PLoS Biol. 18 (7), e3000411 (2020).","journal-title":"PLoS Biol."},{"issue":"Suppl 3","key":"35708_CR29","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.1016\/j.joca.2010.05.025","volume":"18","author":"SS Glasson","year":"2010","unstructured":"Glasson, S. S. et al. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse. Osteoarthr. Cartil. 18 (Suppl 3), S17\u201323 (2010).","journal-title":"Osteoarthr. Cartil."},{"issue":"1","key":"35708_CR30","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s11658-023-00489-y","volume":"28","author":"J Riegger","year":"2023","unstructured":"Riegger, J. et al. Oxidative stress as a key modulator of cell fate decision in osteoarthritis and osteoporosis: a narrative review. Cell. Mol. Biol. Lett. 28 (1), 76 (2023).","journal-title":"Cell. Mol. Biol. Lett."},{"key":"35708_CR31","doi-asserted-by":"publisher","first-page":"2186","DOI":"10.12659\/MSM.911250","volume":"25","author":"M Zhao","year":"2019","unstructured":"Zhao, M. et al. Neuro-Protective role of Metformin in patients with acute stroke and type 2 diabetes mellitus via AMPK\/Mammalian target of Rapamycin (mTOR) signaling pathway and oxidative stress. Med. Sci. Monit. 25, 2186\u20132194 (2019).","journal-title":"Med. Sci. Monit."},{"key":"35708_CR32","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.biochi.2018.08.002","volume":"154","author":"I Dogan Turacli","year":"2018","unstructured":"Dogan Turacli, I. et al. Potential effects of Metformin in DNA BER system based on oxidative status in type 2 diabetes. Biochimie 154, 62\u201368 (2018).","journal-title":"Biochimie"},{"issue":"5","key":"35708_CR33","doi-asserted-by":"publisher","first-page":"367","DOI":"10.3109\/09513590.2014.887063","volume":"30","author":"D Kocer","year":"2014","unstructured":"Kocer, D., Bayram, F. & Diri, H. The effects of Metformin on endothelial dysfunction, lipid metabolism and oxidative stress in women with polycystic ovary syndrome. Gynecol. Endocrinol. 30 (5), 367\u2013371 (2014).","journal-title":"Gynecol. Endocrinol."},{"key":"35708_CR34","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13018-016-0346-5","volume":"11","author":"EL Kuyinu","year":"2016","unstructured":"Kuyinu, E. L. et al. Animal models of osteoarthritis: classification, update, and measurement of outcomes. J. Orthop. Surg. Res. 11, 19 (2016).","journal-title":"J. Orthop. Surg. Res."},{"key":"35708_CR35","doi-asserted-by":"publisher","first-page":"974","DOI":"10.3389\/fphar.2019.00974","volume":"10","author":"S de Valente","year":"2019","unstructured":"de Valente, S. The Pharmacology of pain associated with the monoiodoacetate model of osteoarthritis. Front. Pharmacol. 10, 974 (2019).","journal-title":"Front. Pharmacol."},{"key":"35708_CR36","doi-asserted-by":"publisher","first-page":"42294","DOI":"10.1038\/srep42294","volume":"7","author":"H Huang","year":"2017","unstructured":"Huang, H. et al. Age-dependent changes in the articular cartilage and subchondral bone of C57BL\/6 mice after surgical destabilization of medial meniscus. Sci. Rep. 7, 42294 (2017).","journal-title":"Sci. Rep."},{"issue":"10","key":"35708_CR37","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1002\/art.42530","volume":"75","author":"T Geraghty","year":"2023","unstructured":"Geraghty, T. et al. Age-Associated changes in knee Osteoarthritis, Pain-Related Behaviors, and dorsal root ganglia immunophenotyping of male and female mice. Arthritis Rheumatol. 75 (10), 1770\u20131780 (2023).","journal-title":"Arthritis Rheumatol."},{"key":"35708_CR38","doi-asserted-by":"publisher","first-page":"730","DOI":"10.3389\/fimmu.2020.00730","volume":"11","author":"HS Na","year":"2020","unstructured":"Na, H. S. et al. Interleukin-1-Interleukin-17 signaling axis induces cartilage destruction and promotes experimental osteoarthritis. Front. Immunol. 11, 730 (2020).","journal-title":"Front. Immunol."},{"issue":"5","key":"35708_CR39","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1038\/s41401-021-00747-9","volume":"43","author":"C Fang","year":"2022","unstructured":"Fang, C. et al. Diterbutyl phthalate attenuates osteoarthritis in ACLT mice via suppressing ERK\/c-fos\/NFATc1 pathway, and subsequently inhibiting subchondral osteoclast fusion. Acta Pharmacol. Sin. 43 (5), 1299\u20131310 (2022).","journal-title":"Acta Pharmacol. Sin"},{"key":"35708_CR40","doi-asserted-by":"crossref","unstructured":"Luong, T. N. et al. Assessment of motor balance and coordination in mice using the balance beam. J. Vis. Exp. 49, e2376 (2011).","DOI":"10.3791\/2376-v"},{"issue":"1","key":"35708_CR41","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1186\/s12891-022-05164-5","volume":"23","author":"J Li","year":"2022","unstructured":"Li, J. et al. Ligamentous injury-induced ankle instability causing posttraumatic osteoarthritis in a mouse model. BMC Musculoskelet. Disord. 23 (1), 223 (2022).","journal-title":"BMC Musculoskelet. Disord"},{"key":"35708_CR42","doi-asserted-by":"crossref","unstructured":"Na, H. S. et al. Metformin attenuates Monosodium-Iodoacetate-Induced osteoarthritis via regulation of pain mediators and the Autophagy-Lysosomal pathway. Cells, 10 (3), 642 (2021).","DOI":"10.3390\/cells10030681"},{"issue":"5","key":"35708_CR43","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/j.bbamcr.2008.01.002","volume":"1783","author":"GH Liu","year":"2008","unstructured":"Liu, G. H., Qu, J. & Shen, X. NF-kappaB\/p65 antagonizes Nrf2-ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3 to MafK. Biochim. Biophys. Acta. 1783 (5), 713\u2013727 (2008).","journal-title":"Biochim. Biophys. Acta"},{"issue":"4","key":"35708_CR44","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1089\/ars.2010.3835","volume":"15","author":"N Maicas","year":"2011","unstructured":"Maicas, N. et al. Deficiency of Nrf2 accelerates the effector phase of arthritis and aggravates joint disease. Antioxid. Redox Signal. 15 (4), 889\u2013901 (2011).","journal-title":"Antioxid. Redox Signal."},{"issue":"5","key":"35708_CR45","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1136\/ard.2010.132720","volume":"70","author":"CJ Wruck","year":"2011","unstructured":"Wruck, C. J. et al. Role of oxidative stress in rheumatoid arthritis: insights from the Nrf2-knockout mice. Ann. Rheum. Dis. 70 (5), 844\u2013850 (2011).","journal-title":"Ann. Rheum. Dis."},{"key":"35708_CR46","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.placenta.2023.10.003","volume":"143","author":"L He","year":"2023","unstructured":"He, L. et al. Protective role of Metformin in preeclampsia via the regulation of NF-\u03baB\/sFlt-1 and Nrf2\/HO-1 signaling pathways by activating AMPK. Placenta 143, 91\u201399 (2023).","journal-title":"Placenta"},{"key":"35708_CR47","doi-asserted-by":"publisher","first-page":"121092","DOI":"10.1016\/j.lfs.2022.121092","volume":"312","author":"B Chen","year":"2023","unstructured":"Chen, B. et al. Metformin suppresses oxidative stress induced by high glucose via activation of the Nrf2\/HO-1 signaling pathway in type 2 diabetic osteoporosis. Life Sci. 312, 121092 (2023).","journal-title":"Life Sci."},{"key":"35708_CR48","doi-asserted-by":"publisher","first-page":"1527316","DOI":"10.3389\/fphar.2025.1527316","volume":"16","author":"Y Liu","year":"2025","unstructured":"Liu, Y. et al. Metformin attenuates diabetic osteoporosis by suppressing ferroptosis via the AMPK\/Nrf2 pathway. Front. Pharmacol. 16, 1527316 (2025).","journal-title":"Front. Pharmacol."},{"issue":"19","key":"35708_CR49","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.3390\/cells11193021","volume":"11","author":"B Chhunchha","year":"2022","unstructured":"Chhunchha, B., Kubo, E. & Singh, D. Obligatory role of AMPK activation and antioxidant defense pathway in the regulatory effects of Metformin on cellular protection and prevention of lens opacity. Cells 11 (19), 3021 (2022).","journal-title":"Cells"},{"issue":"3","key":"35708_CR50","doi-asserted-by":"publisher","first-page":"222","DOI":"10.3892\/etm.2022.11146","volume":"23","author":"J Yan","year":"2022","unstructured":"Yan, J. et al. Metformin reduces chondrocyte pyroptosis in an osteoarthritis mouse model by inhibiting NLRP3 inflammasome activation. Exp. Ther. Med. 23 (3), 222 (2022).","journal-title":"Exp. Ther. Med."},{"issue":"2","key":"35708_CR51","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1021\/acs.biomac.0c01488","volume":"22","author":"L Xu","year":"2021","unstructured":"Xu, L. et al. Metformin hydrochloride encapsulation by alginate strontium hydrogel for cartilage regeneration by reliving cellular senescence. Biomacromolecules 22 (2), 671\u2013680 (2021).","journal-title":"Biomacromolecules"},{"issue":"1","key":"35708_CR52","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1515\/biol-2022-0079","volume":"17","author":"Z Bao","year":"2022","unstructured":"Bao, Z. et al. Monosodium iodoacetate-induced subchondral bone microstructure and inflammatory changes in an animal model of osteoarthritis. Open. Life Sci. 17 (1), 781\u2013793 (2022).","journal-title":"Open. Life Sci."},{"key":"35708_CR53","doi-asserted-by":"crossref","unstructured":"Sun et al. Imbalance of Bone Homeostasis Caused by Nrf2 Deficiency Leads to Bone Loss in OVX Rats. Stem Cells Int, 2025, 7214250. (2025).","DOI":"10.1155\/sci\/7214250"},{"key":"35708_CR54","doi-asserted-by":"publisher","first-page":"105787","DOI":"10.1016\/j.jdent.2025.105787","volume":"158","author":"K Dong","year":"2025","unstructured":"Dong, K. et al. Metformin\u2019s mechanism in reducing oxidative stress and promoting bone regeneration in T2DM rat bmmscs: A focus on NRF2-GPX7 signaling pathway. J. Dent. 158, 105787 (2025).","journal-title":"J. Dent."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-35708-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-35708-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-35708-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T11:03:38Z","timestamp":1770289418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-35708-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,10]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["35708"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-35708-x","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,10]]},"assertion":[{"value":"12 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The animal protocol employed in this study was approved by the Animal Experimentation Committee of Jinan University (IACUC-20191212-02).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4966"}}