{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:29:21Z","timestamp":1792182561402,"version":"4.4.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100005145","name":"Basic Research Program of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20240514"],"award-info":[{"award-number":["BK20240514"]}],"id":[{"id":"10.13039\/501100005145","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012154","name":"Graduate Research and Innovation Projects of Jiangsu Province","doi-asserted-by":"publisher","award":["SJCX24_0803"],"award-info":[{"award-number":["SJCX24_0803"]}],"id":[{"id":"10.13039\/501100012154","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jiangsu Province Capability Improvement Project through Science, Technology and Education-Jiangsu Provincial Research Hospital Cultivation Unit","award":["YJXYYJSDW4"],"award-info":[{"award-number":["YJXYYJSDW4"]}]},{"DOI":"10.13039\/100017962","name":"jiangsu commission of health","doi-asserted-by":"publisher","award":["ZD2021025 and BJ19033"],"award-info":[{"award-number":["ZD2021025 and BJ19033"]}],"id":[{"id":"10.13039\/100017962","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jiangsu Provincial Medical Innovation Center","award":["CXZX202227"],"award-info":[{"award-number":["CXZX202227"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370961 and 82170962"],"award-info":[{"award-number":["82370961 and 82170962"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>\n                    Periodontitis has recently been recognized as an inflammatory disease caused by oxidative stress, with mitochondrial dysfunction being a key factor leading to oxidative stress. PTEN-induced kinase 1 (PINK1) is an essential protein for mitochondrial quality control, which protects cells from oxidative stress by inducing mitophagy to degrade damaged mitochondria, but its role in periodontitis has not been elucidated. This study aimed to explore the contribution and underlying mechanisms of Pink1 in regulating the differentiation and function of osteoclasts during periodontitis. Here we observed a significant downregulation of PINK1 expression in periodontitis-affected tissues. Then we constructed a periodontitis model in mice with fluorescently labeled mononuclear\/macrophages, and the results showed that as the modeling time extended, the alveolar bone destruction gradually worsened and was accompanied by gradually decreased Pink1 expression in osteoclasts and a significantly increased osteoclast number. In vitro experiments further demonstrated a negative correlation between Pink1 and osteoclast differentiation. In addition, alveolar bone destruction in the\n                    <jats:italic>Pink1<\/jats:italic>\n                    knockout mice was significantly more advanced than that in the littermate wild type mice after ligature-induced periodontitis and enhanced osteoclastogenesis and bone-resorptive capacity in vitro. RNA-sequencing analysis and in vitro validation revealed that the absence of Pink1 led to a decrease in oxidative phosphorylation levels and an enhancement of calcium-mediated signaling, specifically the calcineurin-NFATc1 pathway, via an intracellular calcium source. Further mechanistic studies found that the deficiency of Pink1 inhibited mitophagy but strengthened mitochondrial\u2013endoplasmic reticulum coupling, which, by promoting the interaction of Mfn2-IP3R-VDAC1 proteins, increased the concentration of mitochondrial calcium ions, thereby triggering more active osteoclast differentiation. The aforementioned process can be reversed by the IP3R channel inhibitor Bcl-XL. These findings unveiled that Pink1 was involved in osteoclast differentiation by regulating mitochondrial calcium transport mediated by mitochondria-associated endoplasmic reticulum membranes, providing a new theoretical basis for the pathogenesis and treatment of periodontitis.\n                  <\/jats:p>","DOI":"10.1177\/00220345251315723","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:50:48Z","timestamp":1741827048000},"page":"753-762","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Role of Pink1 in Regulating Osteoclast Differentiation during Periodontitis"],"prefix":"10.1177","volume":"104","author":[{"given":"H.","family":"Gou","sequence":"first","affiliation":[{"name":"Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China"},{"name":"State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China"},{"name":"State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China"},{"name":"State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8085-0261","authenticated-orcid":false,"given":"Y.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China"},{"name":"State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China"},{"name":"State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9975-2215","authenticated-orcid":false,"given":"Y.","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China"},{"name":"State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900010RR"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2023.122238"},{"key":"e_1_3_2_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.012023"},{"key":"e_1_3_2_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051772"},{"key":"e_1_3_2_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.132826"},{"key":"e_1_3_2_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0329-y"},{"key":"e_1_3_2_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13112"},{"key":"e_1_3_2_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202403177"},{"key":"e_1_3_2_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1850609"},{"issue":"10","key":"e_1_3_2_11_1","first-page":"3149","article-title":"The antiapoptotic protein Bcl-xL negatively regulates the bone-resorbing activity of osteoclasts in mice","volume":"119","author":"Iwasawa M","year":"2009","unstructured":"Iwasawa M, Miyazaki T, Nagase Y, Akiyama T, Kadono Y, Nakamura M, Oshima Y, Yasui T, Matsumoto T, Nakamura T, et al. 2009. The antiapoptotic protein Bcl-xL negatively regulates the bone-resorbing activity of osteoclasts in mice. J Clin Invest. 119(10):3149\u20133159.","journal-title":"J Clin Invest"},{"key":"e_1_3_2_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.103023"},{"key":"e_1_3_2_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-017-0105-5"},{"key":"e_1_3_2_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13963"},{"key":"e_1_3_2_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102635"},{"key":"e_1_3_2_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14286"},{"key":"e_1_3_2_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.13152"},{"key":"e_1_3_2_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21103646"},{"key":"e_1_3_2_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.01.002"},{"key":"e_1_3_2_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.38"},{"key":"e_1_3_2_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06002-x"},{"key":"e_1_3_2_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12519"},{"key":"e_1_3_2_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-017-0027-2"},{"key":"e_1_3_2_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2009.00821.x"},{"key":"e_1_3_2_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.02.035"},{"key":"e_1_3_2_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.001225"},{"key":"e_1_3_2_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-019-00757-0"},{"key":"e_1_3_2_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05634.x"},{"key":"e_1_3_2_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05343-1"},{"key":"e_1_3_2_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12342"},{"key":"e_1_3_2_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12221"},{"key":"e_1_3_2_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1986.tb02220.x"},{"key":"e_1_3_2_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1822097"},{"key":"e_1_3_2_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01157-7"},{"key":"e_1_3_2_35_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.46627"},{"key":"e_1_3_2_36_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345221138523"},{"key":"e_1_3_2_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2048432"},{"key":"e_1_3_2_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154967"},{"key":"e_1_3_2_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1975914"},{"key":"e_1_3_2_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-020-00731-6"},{"key":"e_1_3_2_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.321200"}],"container-title":["Journal of Dental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345251315723","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/00220345251315723","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345251315723","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:09:12Z","timestamp":1777496952000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/00220345251315723"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,12]]},"references-count":40,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1177\/00220345251315723"],"URL":"https:\/\/doi.org\/10.1177\/00220345251315723","relation":{},"ISSN":["0022-0345","1544-0591"],"issn-type":[{"value":"0022-0345","type":"print"},{"value":"1544-0591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,12]]}}}