Evidence map›Paper›PMID 42622979›Full record

ArticleJournal of biochemical and molecular toxicology2026

2-Hydroxyethyl Methacrylate Increases MMP-1 and MMP-3 Production in Human Gingival Fibroblasts.

Risa Okamoto, Yoshitaka Hosokawa, Ikuko Hosokawa, Ai Fukui, Natsuho Miyake, Kazumi Ozaki, Keiichi Hosaka

Abstract read
In one paragraph

Article in Journal of biochemical and molecular toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Risa OkamotoDepartment of Conservative Dentistry, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Yoshitaka HosokawaDepartment of Conservative Dentistry, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.ORCID https://orcid.org/0000-0002-4526-4902
Ikuko HosokawaDepartment of Conservative Dentistry, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Ai FukuiDepartment of Conservative Dentistry, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Natsuho MiyakeDepartment of Conservative Dentistry, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Kazumi OzakiDepartment of Oral Health Care Promotion, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Keiichi HosakaDepartment of Conservative Dentistry, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.ORCID https://orcid.org/0000-0002-8471-358X

Funding

Japan Society for the Promotion of Science 22K09966Japan Society for the Promotion of Science 22K09984The NSK Nakanishi FoundationUniversity of Tokushima 2202006
6 · The paper itself

Abstract

2-Hydroxyethyl 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-inflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8), as well as matrix metalloproteinases (MMP)-1 and MMP-3, 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-6 or IL-8 production, but significantly increased MMP-1 and MMP-3 levels in a concentration-dependent manner. In contrast, tissue inhibitor of metalloproteinases (TIMP)-1 production was suppressed by HEMA. Moreover, compared with 24-h exposure, 48-h exposure induced increases in MMP production and decreases in TIMP-1 production at lower concentrations of HEMA. Furthermore, HEMA enhanced the phosphorylation of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and protein kinase B (Akt). Inhibitor studies revealed that the p38 MAPK, extracellular signal-regulated kinase (ERK), JNK, and Akt signaling pathways are involved in the regulation of MMP-1 and MMP-3 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-curable resin materials and thorough removal of excess resin cement. The use of HEMA-free materials may also be worth considering to minimize biological risks.

Indexed as

FibroblastsGingivaMatrix Metalloproteinase 1Matrix Metalloproteinase 3MethacrylatesCells, CulturedHumansInterleukin-6Interleukin-8MAP Kinase Signaling SystemTissue Inhibitor of Metalloproteinase-1hydroxyethyl methacrylateInterleukin-6Interleukin-8Matrix Metalloproteinase 1Matrix Metalloproteinase 3MethacrylatesMMP1 protein, humanMMP3 protein, humanTissue Inhibitor of Metalloproteinase-12‐hydroxyethyl methacrylategingival fibroblastMAPKsMMP‐1MMP‐3

Identifiers

PMID42622979
PMCPMC13492507

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.