{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:06:40Z","timestamp":1791846400022,"version":"4.3.4"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Tianjin Stomatological Hospital"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Oral Health"],"DOI":"10.1186\/s12903-026-08251-4","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T03:48:38Z","timestamp":1775447318000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Therapeutic potential of low-dose rosiglitazone in periodontitis: attenuation of inflammation and bone loss through macrophage reprogramming"],"prefix":"10.1186","volume":"26","author":[{"given":"Li-Na","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"8251_CR1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s12010-022-04127-9","volume":"195","author":"RR Ray","year":"2023","unstructured":"Ray RR, Periodontitis. An oral disease with severe consequences. Appl Biochem Biotechnol. 2023;195:17\u201332.","journal-title":"Appl Biochem Biotechnol"},{"key":"8251_CR2","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1111\/jcpe.12732","volume":"44","author":"MS Tonetti","year":"2017","unstructured":"Tonetti MS, Jepsen S, Jin L, Otomo-Corgel J. Impact of the global burden of periodontal diseases on health, nutrition and wellbeing of mankind: A call for global action. J Clin Periodontol. 2017;44:456\u201362.","journal-title":"J Clin Periodontol"},{"key":"8251_CR3","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1002\/JPER.21-0111","volume":"93","author":"J Botelho","year":"2022","unstructured":"Botelho J, et al. Economic burden of periodontitis in the united states and europe: An updated estimation. J Periodontol. 2022;93:373\u20139.","journal-title":"J Periodontol"},{"key":"8251_CR4","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1111\/idj.12630","volume":"71","author":"T Kwon","year":"2021","unstructured":"Kwon T, Lamster IB, Levin L. Current concepts in the management of periodontitis. Int Dent J. 2021;71:462\u201376.","journal-title":"Int Dent J"},{"key":"8251_CR5","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1111\/prd.12032","volume":"63","author":"C Sima","year":"2013","unstructured":"Sima C, Glogauer M. Macrophage subsets and osteoimmunology: Tuning of the immunological recognition and effector systems that maintain alveolar bone. Periodontol 2000. 2013;63:80\u2013101.","journal-title":"Periodontol 2000"},{"key":"8251_CR6","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1007\/s10266-024-00935-z","volume":"112","author":"M Shi","year":"2024","unstructured":"Shi M, et al. Role of macrophage polarization in periodontitis promoting atherosclerosis. Odontology. 2024;112:1209\u201320.","journal-title":"Odontology"},{"key":"8251_CR7","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1186\/s12967-024-05214-7","volume":"22","author":"L Zhang","year":"2024","unstructured":"Zhang L, et al. PGRN is involved in macrophage M2 polarization regulation through TNFR2 in periodontitis. J Transl Med. 2024;22:407.","journal-title":"J Transl Med"},{"key":"8251_CR8","doi-asserted-by":"publisher","first-page":"114345","DOI":"10.1016\/j.intimp.2025.114345","volume":"151","author":"S Jafarzadeh","year":"2025","unstructured":"Jafarzadeh S, Nemati M, Zandvakili R, Jafarzadeh A. Modulation of M1 and M2 macrophage polarization by metformin: Implications for inflammatory diseases and malignant tumors. Int Immunopharmacol. 2025;151:114345.","journal-title":"Int Immunopharmacol"},{"key":"8251_CR9","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1007\/s10753-024-02015-4","volume":"47","author":"W Luo","year":"2024","unstructured":"Luo W, et al. The role of macrophage death in periodontitis: A review. Inflammation. 2024;47:1889\u2013901.","journal-title":"Inflammation"},{"key":"8251_CR10","doi-asserted-by":"crossref","unstructured":"Arango Duque G, Descoteaux A. Macrophage cytokines: Involvement in immunity and infectious diseases. Front Immunol 5, (2014).","DOI":"10.3389\/fimmu.2014.00491"},{"key":"8251_CR11","doi-asserted-by":"publisher","first-page":"7119","DOI":"10.1073\/pnas.0902745106","volume":"106","author":"SZ Ben-Sasson","year":"2009","unstructured":"Ben-Sasson SZ, et al. IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation. Proc Natl Acad Sci. 2009;106:7119\u201324.","journal-title":"Proc Natl Acad Sci"},{"key":"8251_CR12","doi-asserted-by":"publisher","first-page":"3815","DOI":"10.4049\/jimmunol.147.11.3815","volume":"147","author":"DF Fiorentino","year":"1991","unstructured":"Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O\u2019Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991;147:3815\u201322.","journal-title":"J Immunol"},{"key":"8251_CR13","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1177\/0022034520910127","volume":"99","author":"X Wu","year":"2020","unstructured":"Wu X, Chen H, Wang Y, Gu Y. Akt2 affects periodontal inflammation via altering the M1\/M2 ratio. J Dent Res. 2020;99:577\u201387.","journal-title":"J Dent Res"},{"key":"8251_CR14","doi-asserted-by":"crossref","unstructured":"Hasturk H, Kantarci A, Van Dyke TE. Oral inflammatory diseases and systemic inflammation: Role of the macrophage. Front Immunol 3, (2012).","DOI":"10.3389\/fimmu.2012.00118"},{"key":"8251_CR15","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/83328","volume":"7","author":"KJ Moore","year":"2001","unstructured":"Moore KJ, et al. The role of PPAR-\u03b3 in macrophage differentiation and cholesterol uptake. Nat Med. 2001;7:41\u20137.","journal-title":"Nat Med"},{"key":"8251_CR16","doi-asserted-by":"publisher","first-page":"116908","DOI":"10.1016\/j.bcp.2025.116908","volume":"237","author":"IG Nicchio","year":"2025","unstructured":"Nicchio IG, et al. Understanding the peroxisome proliferator-activated receptor gamma (PPAR-\u03b3) role in periodontitis and diabetes mellitus: A molecular perspective. Biochem Pharmacol. 2025;237:116908.","journal-title":"Biochem Pharmacol"},{"key":"8251_CR17","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/s11892-019-1270-y","volume":"19","author":"HE Lebovitz","year":"2019","unstructured":"Lebovitz HE, Thiazolidinediones. The forgotten diabetes medications. Curr Diab Rep. 2019;19:151.","journal-title":"Curr Diab Rep"},{"key":"8251_CR18","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.cmet.2007.06.010","volume":"6","author":"MA Bouhlel","year":"2007","unstructured":"Bouhlel MA, et al. PPAR\u03b3 activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab. 2007;6:137\u201343.","journal-title":"Cell Metab"},{"key":"8251_CR19","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1177\/154405910608500208","volume":"85","author":"R Di Paola","year":"2006","unstructured":"Di Paola R, et al. Rosiglitazone reduces the evolution of experimental periodontitis in the rat. J Dent Res. 2006;85:156\u201361.","journal-title":"J Dent Res"},{"key":"8251_CR20","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.bone.2016.06.011","volume":"90","author":"A Soundia","year":"2016","unstructured":"Soundia A, et al. Osteonecrosis of the jaws (ONJ) in mice after extraction of teeth with periradicular disease. Bone. 2016;90:133\u201341.","journal-title":"Bone"},{"key":"8251_CR21","doi-asserted-by":"publisher","first-page":"23517","DOI":"10.1074\/jbc.M111.324814","volume":"287","author":"A Mieczkowska","year":"2012","unstructured":"Mieczkowska A, Basl\u00e9 MF, Chappard D, Mabilleau G. Thiazolidinediones induce osteocyte apoptosis by a G protein-coupled receptor 40-dependent mechanism. J Biol Chem. 2012;287:23517\u201326.","journal-title":"J Biol Chem"},{"key":"8251_CR22","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1111\/j.1464-5491.2010.03048.x","volume":"27","author":"G Mabilleau","year":"2010","unstructured":"Mabilleau G, Mieczkowska A, Edmonds ME. Thiazolidinediones induce osteocyte apoptosis and increase sclerostin expression. Diabet Med. 2010;27:925\u201332.","journal-title":"Diabet Med"},{"key":"8251_CR23","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.1016\/j.joen.2017.06.026","volume":"43","author":"KMH De Oliveira","year":"2017","unstructured":"De Oliveira KMH, et al. Effects of rosiglitazone on the outcome of experimental periapical lesions in mice. J Endod. 2017;43:2061\u20139.","journal-title":"J Endod"},{"key":"8251_CR24","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1902\/jop.2012.110540","volume":"84","author":"K Saadi-Thiers","year":"2013","unstructured":"Saadi-Thiers K, et al. Periodontal and systemic responses in various mice models of experimental periodontitis: Respective roles of inflammation duration and porphyromonas gingivalis infection. J Periodontol. 2013;84:396\u2013406.","journal-title":"J Periodontol"},{"key":"8251_CR25","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1902\/jop.2016.160081","volume":"87","author":"T Yu","year":"2016","unstructured":"Yu T, et al. Enhanced activity of the macrophage M1\/M2 phenotypes and phenotypic switch to M1 in periodontal infection. J Periodontol. 2016;87:1092\u2013102.","journal-title":"J Periodontol"},{"key":"8251_CR26","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1186\/s12951-024-02592-4","volume":"22","author":"S Peng","year":"2024","unstructured":"Peng S, et al. A new direction in periodontitis treatment: Biomaterial-mediated macrophage immunotherapy. J Nanobiotechnol. 2024;22:359.","journal-title":"J Nanobiotechnol"},{"key":"8251_CR27","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1111\/odi.12983","volume":"25","author":"L Zhou","year":"2019","unstructured":"Zhou L, et al. Macrophage polarization in human gingival tissue in response to periodontal disease. Oral Dis. 2019;25:265\u201373.","journal-title":"Oral Dis"},{"key":"8251_CR28","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1177\/00220345241258990","volume":"103","author":"A Soundia","year":"2024","unstructured":"Soundia A, et al. Macrophage polarization during MRONJ development in mice. J Dent Res. 2024;103:899\u2013907.","journal-title":"J Dent Res"},{"key":"8251_CR29","doi-asserted-by":"publisher","first-page":"117738","DOI":"10.1016\/j.jep.2024.117738","volume":"323","author":"Y Wu","year":"2024","unstructured":"Wu Y, et al. A breakthrough in periodontitis treatment: Revealing the pharmacodynamic substances and mechanisms of kouqiangjie formula. J Ethnopharmacol. 2024;323:117738.","journal-title":"J Ethnopharmacol"},{"key":"8251_CR30","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1111\/jre.12754","volume":"55","author":"O Karatas","year":"2020","unstructured":"Karatas O, et al. Cinnamic acid decreases periodontal inflammation and alveolar bone loss in experimental periodontitis. J Periodontal Res. 2020;55:676\u201385.","journal-title":"J Periodontal Res"},{"key":"8251_CR31","doi-asserted-by":"publisher","first-page":"269","DOI":"10.4103\/njcp.njcp_216_20","volume":"24","author":"O Karatas","year":"2021","unstructured":"Karatas O, et al. Detection of nuclear receptors in gingival samples of diabetic and nondiabetic periodontitis patients. Niger J Clin Pract. 2021;24:269\u201376.","journal-title":"Niger J Clin Pract"},{"key":"8251_CR32","doi-asserted-by":"publisher","first-page":"46","DOI":"10.4103\/njcp.njcp_349_19","volume":"23","author":"M Taskan","year":"2020","unstructured":"Taskan M, Gevrek F, PPAR-\u03b3 RXR. COX-2 expressions in gingival tissue samples of healthy individuals, periodontitis and peri-implantitis patients. Niger J Clin Pract. 2020;23:46.","journal-title":"Niger J Clin Pract"},{"key":"8251_CR33","doi-asserted-by":"publisher","first-page":"580","DOI":"10.21037\/atm-22-2207","volume":"10","author":"L Qian","year":"2022","unstructured":"Qian L, Yin X, Lan T, Lu Y. Peroxisome proliferator-activated receptor gamma preserves intracellular homeostasis of insulin-resistant periodontal ligament stem cells. Ann Transl Med. 2022;10:580\u2013580.","journal-title":"Ann Transl Med"},{"key":"8251_CR34","doi-asserted-by":"publisher","first-page":"753194","DOI":"10.3389\/fcell.2021.753194","volume":"9","author":"M Chen","year":"2021","unstructured":"Chen M, Lin W, Ye R, Yi J, Zhao Z. PPAR\u03b2\/\u03b4 agonist alleviates diabetic osteoporosis via regulating M1\/M2 macrophage polarization. Front Cell Dev Biol. 2021;9:753194.","journal-title":"Front Cell Dev Biol"},{"key":"8251_CR35","doi-asserted-by":"publisher","first-page":"102510","DOI":"10.1016\/j.jaut.2020.102510","volume":"113","author":"Y Liu","year":"2020","unstructured":"Liu Y, Wang J, Luo S, Zhan Y, Lu Q. The roles of PPAR\u03b3 and its agonists in autoimmune diseases: A comprehensive review. J Autoimmun. 2020;113:102510.","journal-title":"J Autoimmun"},{"key":"8251_CR36","doi-asserted-by":"publisher","first-page":"115913","DOI":"10.1016\/j.bone.2021.115913","volume":"147","author":"S Baroi","year":"2021","unstructured":"Baroi S, Czernik PJ, Chougule A, Griffin PR, Lecka-Czernik B. PPARG in osteocytes controls sclerostin expression, bone mass, marrow adiposity and mediates TZD-induced bone loss. Bone. 2021;147:115913.","journal-title":"Bone"},{"key":"8251_CR37","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1210\/en.2004-0735","volume":"146","author":"AA Ali","year":"2005","unstructured":"Ali AA, et al. Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation. Endocrinology. 2005;146:1226\u201335.","journal-title":"Endocrinology"},{"key":"8251_CR38","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1677\/joe.1.05723","volume":"183","author":"MA Soroc\u00e9anu","year":"2004","unstructured":"Soroc\u00e9anu MA, et al. Rosiglitazone impacts negatively on bone by promoting osteoblast\/osteocyte apoptosis. J Endocrinol. 2004;183:203\u201316.","journal-title":"J Endocrinol"},{"key":"8251_CR39","doi-asserted-by":"publisher","first-page":"e1285","DOI":"10.1002\/osi2.1285","volume":"22","author":"R Kubo","year":"2025","unstructured":"Kubo R, et al. Differences in alveolar bone mineral density by tooth type in female osteoporotic patients treated with bisphosphonates. Oral Sci Int. 2025;22:e1285.","journal-title":"Oral Sci Int"},{"key":"8251_CR40","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1186\/s12903-025-05735-7","volume":"25","author":"G Zhang","year":"2025","unstructured":"Zhang G, et al. From teeth to bone: Dental caries has causal effects on osteoporosis and osteoporotic fracture. BMC Oral Health. 2025;25:340.","journal-title":"BMC Oral Health"},{"key":"8251_CR41","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1172\/JCI200316575","volume":"111","author":"AP Heaney","year":"2003","unstructured":"Heaney AP, Fernando M, Melmed S. PPAR-\u03b3 receptor ligands: Novel therapy for pituitary adenomas. J Clin Invest. 2003;111:1381\u20138.","journal-title":"J Clin Invest"},{"key":"8251_CR42","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1055\/s-0040-1712718","volume":"14","author":"DE Ramadan","year":"2020","unstructured":"Ramadan DE, Hariyani N, Indrawati R, Ridwan RD, Diyatri I. Cytokines and chemokines in periodontitis. Eur J Dent. 2020;14:483\u201395.","journal-title":"Eur J Dent"},{"key":"8251_CR43","doi-asserted-by":"publisher","first-page":"691013","DOI":"10.3389\/fimmu.2021.691013","volume":"12","author":"Y Li","year":"2021","unstructured":"Li Y, Ling J, Jiang Q. Inflammasomes in alveolar bone loss. Front Immunol. 2021;12:691013.","journal-title":"Front Immunol"},{"key":"8251_CR44","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1111\/jcpe.13258","volume":"47","author":"J Zhang","year":"2020","unstructured":"Zhang J, et al. NLRP3 inflammasome mediates M1 macrophage polarization and IL-1\u03b2 production in inflammatory root resorption. J Clin Periodontol. 2020;47:451\u201360.","journal-title":"J Clin Periodontol"},{"key":"8251_CR45","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/s12951-022-01314-y","volume":"20","author":"X Chen","year":"2022","unstructured":"Chen X, et al. Exosomes derived from reparative M2-like macrophages prevent bone loss in murine periodontitis models via IL-10 mRNA. J Nanobiotechnol. 2022;20:110.","journal-title":"J Nanobiotechnol"},{"key":"8251_CR46","doi-asserted-by":"publisher","first-page":"3591","DOI":"10.1111\/jcmm.17399","volume":"26","author":"F Huang","year":"2022","unstructured":"Huang F, et al. Osteoimmunology: The correlation between osteoclasts and the Th17\/treg balance in osteoporosis. J Cell Mol Med. 2022;26:3591\u20137.","journal-title":"J Cell Mol Med"},{"key":"8251_CR47","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1002\/2211-5463.12513","volume":"8","author":"K Park","year":"2018","unstructured":"Park K, Oh D, Kim Y, Song K, Ahn D. Rosiglitazone suppresses RANKL-induced NFATc1 autoamplification by disrupting the physical interaction between NFATc1 and PPAR\u03b3. FEBS Open Bio. 2018;8:1584\u201393.","journal-title":"FEBS Open Bio"}],"container-title":["BMC Oral Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12903-026-08251-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12903-026-08251-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12903-026-08251-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T13:03:47Z","timestamp":1776431027000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12903-026-08251-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,6]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8251"],"URL":"https:\/\/doi.org\/10.1186\/s12903-026-08251-4","relation":{},"ISSN":["1472-6831"],"issn-type":[{"value":"1472-6831","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,6]]},"assertion":[{"value":"10 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 April 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":"All experimental procedures involving animals were conducted in strict accordance with the principles of the Basel Declaration and were approved by the Medical Ethics Committee of Tianjin Stomatological Hospital (Approval No. PH2019-B-008). As all animals were purchased from a licensed commercial breeder, informed consent from an animal owner was not required for this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"This article does not contain any studies with human participants performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"697"}}