{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:08:22Z","timestamp":1789549702599,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K09966"],"award-info":[{"award-number":["22K09966"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K09984"],"award-info":[{"award-number":["22K09984"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>2\u2010Hydroxyethyl methacrylate (HEMA), a monomer commonly used in dental resin materials, has been reported to leach from polymerized resins. However, its potential impact on periodontal tissues remains insufficiently understood. This study investigates the effects of HEMA on human gingival fibroblasts (HGFs), which constitute a major component of periodontal connective tissue. Specifically, we examined whether HEMA induces the production of pro\u2010inflammatory cytokines interleukin\u20106 (IL\u20106) and interleukin\u20108 (IL\u20108), as well as matrix metalloproteinases (MMP)\u20101 and MMP\u20103, which are involved in collagen degradation. Furthermore, we analyzed the intracellular signaling pathways activated by HEMA exposure to elucidate the molecular mechanisms underlying these responses. Cytokine and MMP production were analyzed using the ELISA. In addition, activation of intracellular signaling pathways were examined by Western blot analysis. HEMA treatment did not induce IL\u20106 or IL\u20108 production, but significantly increased MMP\u20101 and MMP\u20103 levels in a concentration\u2010dependent manner. In contrast, tissue inhibitor of metalloproteinases (TIMP)\u20101 production was suppressed by HEMA. Moreover, compared with 24\u2010h exposure, 48\u2010h exposure induced increases in MMP production and decreases in TIMP\u20101 production at lower concentrations of HEMA. Furthermore, HEMA enhanced the phosphorylation of p38 mitogen\u2010activated protein kinase (MAPK), c\u2010Jun N\u2010terminal kinase (JNK), and protein kinase B (Akt). Inhibitor studies revealed that the p38 MAPK, extracellular signal\u2010regulated kinase (ERK), JNK, and Akt signaling pathways are involved in the regulation of MMP\u20101 and MMP\u20103 production. These findings suggest that HEMA leaching from resin materials may contribute to periodontal tissue destruction by promoting MMP production in HGFs through activation of specific signaling pathways. Given the potential impact of HEMA on periodontal tissues, it is important to ensure complete polymerization of light\u2010curable resin materials and thorough removal of excess resin cement. The use of HEMA\u2010free materials may also be worth considering to minimize biological risks.<\/jats:p>","DOI":"10.1002\/jbt.71083","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:07:55Z","timestamp":1787238475000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["2\u2010Hydroxyethyl Methacrylate Increases MMP\u20101 and MMP\u20103 Production in Human Gingival Fibroblasts"],"prefix":"10.1002","volume":"40","author":[{"given":"Risa","family":"Okamoto","sequence":"first","affiliation":[{"name":"Department of Conservative Dentistry Tokushima University Graduate School of Biomedical Sciences Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4526-4902","authenticated-orcid":false,"given":"Yoshitaka","family":"Hosokawa","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry Tokushima 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