{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:22:50Z","timestamp":1790713370738,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T00:00:00Z","timestamp":1760832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Research Funds for the Central Universities, Xi\u2019an Jiaotong University","award":["xzy012024106"],"award-info":[{"award-number":["xzy012024106"]}]},{"name":"Fundamental Research Funds for the Central Universities, Xi\u2019an Jiaotong University","award":["xzy022025080"],"award-info":[{"award-number":["xzy022025080"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aimed to elucidate the role of peroxisome proliferator-activated receptor-\u03b3 (PPAR-\u03b3) in regulating macrophage efferocytosis during the pathogenesis of chronic apical periodontitis (CAP). Clinical specimens, rat periapical lesion models, and an in vitro model simulating the CAP inflammatory milieu were employed to examine the contribution of PPAR-\u03b3 to efferocytosis throughout disease progression. The expression of PPAR-\u03b3 in vivo was assessed by single-cell RNA sequencing and immunohistochemical (IHC) staining. Pearson\u2019s correlation and linear trend tests were conducted to investigate the association between PPAR-\u03b3 and macrophage efferocytosis during CAP progression. Pharmacological modulation of PPAR-\u03b3 was further conducted using rosiglitazone (RSG) as an agonist and GW9662 as an antagonist, followed by an assessment of efferocytosis-related parameters and inflammatory responses. Both clinical specimens and animal models demonstrated a progressive reduction in PPAR-\u03b3 expression and macrophage efferocytosis during CAP. Notably, PPAR-\u03b3 attenuated efferocytosis impairment and significantly reduced pathogen-induced inflammatory responses in macrophages. These findings indicate that defective macrophage efferocytosis contributes to the exacerbation of CAP severity, whereas targeting PPAR-\u03b3 may represent a promising therapeutic strategy to alleviate inflammation in periapical lesions by restoring efferocytic capacity. Collectively, this study highlights PPAR-\u03b3 as a potential therapeutic target warranting further investigation in CAP treatment.<\/jats:p>","DOI":"10.3390\/ijms262010157","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T08:18:54Z","timestamp":1760948334000},"page":"10157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["PPAR-\u03b3 Inhibits Chronic Apical Periodontitis by Facilitating Macrophage Efferocytosis"],"prefix":"10.3390","volume":"26","author":[{"given":"Yuting","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"},{"name":"Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"},{"name":"Department of Cariology and Endodontics, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingfei","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"},{"name":"Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"},{"name":"Department of Cariology and Endodontics, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Jia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"},{"name":"Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"},{"name":"Department of Cariology and Endodontics, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"},{"name":"Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"},{"name":"Department of Cariology and Endodontics, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"},{"name":"Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"},{"name":"Department of Cariology and Endodontics, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiezhou","family":"Hou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"},{"name":"Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"},{"name":"Department of Cariology and Endodontics, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyue","family":"Guan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"},{"name":"Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"},{"name":"Department of Cariology and Endodontics, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.freeradbiomed.2023.08.020","article-title":"Ferroptosis of macrophages facilitates bone loss in apical periodontitis via NRF2\/FSP1\/ROS pathway","volume":"208","author":"Yang","year":"2023","journal-title":"Free Radic. 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