{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:06:05Z","timestamp":1789171565757,"version":"build-2803163510"},"reference-count":78,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515012777"],"award-info":[{"award-number":["2023A1515012777"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pulpitis, a prevalent inflammatory dental disease, primarily results from bacterial infection, yet its epigenetic regulatory mechanisms remain poorly understood. PIWI\u2010interacting RNAs (piRNAs), a class of small non\u2010coding RNAs known to maintain genomic stability, have not been investigated in the context of pulpitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to profile piRNA expression patterns in pulpitis and to elucidate the functional role and underlying mechanism of a specific piRNA, piR\u201036241 and its target gene ADGRG2 in disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>piRNA and mRNA sequencing were performed on pulp tissues from patients with irreversible pulpitis and healthy controls. Potential piRNA targets were predicted bioinformatically. The interaction between piR\u201036241 and the 3\u2032UTR of ADGRG2, an orphan adhesion G protein\u2010coupled receptor (GPCR), was validated using dual\u2010luciferase reporter assay, quantitative Real\u2010Time PCR (qRT\u2010PCR), fluorescence in\u00a0situ hybridization (FISH), Western blot (WB), hematoxylin\u2010eosin staining (HE),\u00a0immunohistochemistry (IHC) and enzyme\u2010linked immunosorbent assay (ELISA). Functional analyses were conducted in LPS\u2010stimulated human dental pulp cells (HDPCs) through gain\u2010of\u2010function and rescue experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified a distinct piRNA expression profile in pulpitis, with 21 piRNAs differentially expressed. piR\u201036241 was notably upregulated. It directly targeted the 3\u2032UTR of ADGRG2 and suppressed its expression. ADGRG2, hypothesised to exert protective and homeostatic functions, was downregulated in pulpitis tissues and LPS\u2010induced HDPCs. Overexpression of piR\u201036241 inhibited ADGRG2 expression and promoted the secretion of pro\u2010inflammatory cytokines (IL\u20106, IL\u20108). Conversely, knockdown of ADGRG2 similarly enhanced inflammatory responses. Rescue experiments demonstrated that piR\u201036241 primarily regulates inflammation through ADGRG2 silencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study reveals a novel pathogenic axis in pulpitis whereby upregulation of piR\u201036241 exacerbates inflammatory progression by repressing the protective receptor ADGRG2. These findings provide the first evidence of piRNA\u2010mediated epigenetic regulation in pulpitis and highlight the piR\u201036241\/ADGRG2 pathway as a potential therapeutic target for preserving pulp vitality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.70199","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T09:12:34Z","timestamp":1781514754000},"page":"2164-2179","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel\n                    <scp>piRNA<\/scp>\n                    \u2010Mediated Epigenetic Axis:\n                    <scp>piR<\/scp>\n                    \u201036241 Exacerbates Pulpitis by Silencing the Protective Receptor\n                    <scp>ADGRG2<\/scp>\n                    in Human Dental Pulp Stem Cells"],"prefix":"10.1111","volume":"59","author":[{"given":"Wenmian","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Endodontics School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction &amp; Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Chen","sequence":"additional","affiliation":[{"name":"Shiyan Key Laboratory of Comprehensive Prevention and Treatment of Oral Cancer, Department of Stomatology Taihe Hospital, Hubei University of Medicine  Shiyan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Endodontics School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction &amp; Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mianfeng","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Endodontics School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction &amp; Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Endodontics School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction &amp; Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9212-8890","authenticated-orcid":false,"given":"Xuechao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Endodontics School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction &amp; Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13922"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3023"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-024-04972-6"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004770-200003000-00012"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.70017"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21020521"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34083-1"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1540313"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004770-200402000-00006"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/v17060764"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2025.08.010"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13917"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.12030"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2023.08.019"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/0113894501298344240507080149"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2025.102060"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-025-01503-3"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364400"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.145674"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmaf023"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101231"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16140"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.identj.2025.02.016"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.identj.2025.100958"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2025.08.011"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2591.2012.02096.x"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2016.09.003"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdent.2021.103937"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02830"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.identj.2025.100933"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2017.09.002"},{"key":"e_1_2_11_33_1","first-page":"33","article-title":"PIWI\u2010Interacting RNA: Its Biogenesis and Functions","volume":"84405","author":"Iwasaki Y. 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