{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:41:35Z","timestamp":1791218495880,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T00:00:00Z","timestamp":1545004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["NSC102-2314-B-255-003-MY2, NSC102-2628-B-255-001-MY3, NSC101-2320-B-255-002, NSC-100-2314-B-002-094, NSC-101-2320- B-255-002, MOST104-2314-B-255-010-MY3, MOST106-2314-B-002-034-MY2, and MOST106- 2314-B-002-033-MY2"],"award-info":[{"award-number":["NSC102-2314-B-255-003-MY2, NSC102-2628-B-255-001-MY3, NSC101-2320-B-255-002, NSC-100-2314-B-002-094, NSC-101-2320- B-255-002, MOST104-2314-B-255-010-MY3, MOST106-2314-B-002-034-MY2, and MOST106- 2314-B-002-033-MY2"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPF1H0061, CMRPF1F0071, CMRPF1G0101, CMRPF1G0102, CMRPF3E0021, CMRPF3E0022, CMRPF3E0023, NMRPF3C0091, NMRPF3C0061, CMRPG1B0031, CMRPF170053, NMRPF370033, CMRPF3E0021, NMRPF3B0071, NMRPF3E0041, NMRPF3E0042, NMRPF3E0043, NMRPF3C0093, NMRPF3H0071, NMRPF3H0"],"award-info":[{"award-number":["CMRPF1H0061, CMRPF1F0071, CMRPF1G0101, CMRPF1G0102, CMRPF3E0021, CMRPF3E0022, CMRPF3E0023, NMRPF3C0091, NMRPF3C0061, CMRPG1B0031, CMRPF170053, NMRPF370033, CMRPF3E0021, NMRPF3B0071, NMRPF3E0041, NMRPF3E0042, NMRPF3E0043, NMRPF3C0093, NMRPF3H0071, NMRPF3H0"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005762","name":"National Taiwan University Hospital","doi-asserted-by":"publisher","award":["NTUH 101-001937, NTUH102-002259, NTUH101-S1862 & NTUH102-S2180, NTUH103-S2368, NTUH104-S2658, NTUH106-S3467, NTUH106-UN-001"],"award-info":[{"award-number":["NTUH 101-001937, NTUH102-002259, NTUH101-S1862 & NTUH102-S2180, NTUH103-S2368, NTUH104-S2658, NTUH106-S3467, NTUH106-UN-001"]}],"id":[{"id":"10.13039\/501100005762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Butyric acid as a histone deacetylase (HDAC) inhibitor is produced by a number of periodontal and root canal microorganisms (such as Porphyromonas, Fusobacterium, etc.). Butyric acid may affect the biological activities of periodontal\/periapical cells such as osteoblasts, periodontal ligament cells, etc., and thus affect periodontal\/periapical tissue destruction and healing. The purposes of this study were to study the toxic effects of butyrate on the matrix and mineralization marker expression in MG-63 osteoblasts. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cellular apoptosis and necrosis were analyzed by propidium iodide\/annexin V flow cytometry. The protein and mRNA expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) were analyzed by Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). OPG, soluble RANKL (sRANKL), 8-isoprostane, pro-collagen I, matrix metalloproteinase-2 (MMP-2), osteonectin (SPARC), osteocalcin and osteopontin (OPN) secretion into culture medium were measured by enzyme-linked immunosorbant assay. Alkaline phosphatase (ALP) activity was checked by ALP staining. Histone H3 acetylation levels were evaluated by immunofluorescent staining (IF) and Western blot. We found that butyrate activated the histone H3 acetylation of MG-63 cells. Exposure of MG-63 cells to butyrate partly decreased cell viability with no marked increase in apoptosis and necrosis. Twenty-four hours of exposure to butyrate stimulated RANKL protein expression, whereas it inhibited OPG protein expression. Butyrate also inhibited the secretion of OPG in MG-63 cells, whereas the sRANKL level was below the detection limit. However, 3 days of exposure to butyrate (1 to 8 mM) or other HDAC inhibitors such as phenylbutyrate, valproic acid and trichostatin stimulated OPG secretion. Butyrate stimulated 8-isoprostane, MMP-2 and OPN secretion, but not procollagen I, or osteocalcin in MG-63 cells. Exposure to butyrate (2\u20134 mM) for 3 days markedly stimulated osteonectin secretion and ALP activity. In conclusion, higher concentrations of butyric acid generated by periodontal and root canal microorganisms may potentially induce bone destruction and impair bone repair by the alteration of OPG\/RANKL expression\/secretion, 8-isoprostane, MMP-2 and OPN secretion, and affect cell viability. However, lower concentrations of butyrate (1\u20134 mM) may stimulate ALP, osteonectin and OPG. These effects are possibly related to increased histone acetylation. These events are important in the pathogenesis and repair of periodontal and periapical destruction.<\/jats:p>","DOI":"10.3390\/ijms19124071","type":"journal-article","created":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T02:15:59Z","timestamp":1545099359000},"page":"4071","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Butyrate Stimulates Histone H3 Acetylation, 8-Isoprostane Production, RANKL Expression, and Regulated Osteoprotegerin Expression\/Secretion in MG-63 Osteoblastic Cells"],"prefix":"10.3390","volume":"19","author":[{"given":"Mei-Chi","family":"Chang","sequence":"first","affiliation":[{"name":"Chang Gung University of Science and Technology, Kwei-Shan, Taoyuan 333, Taiwan"},{"name":"Department of Dentistry, Chang Gung Memorial Hospital, Taipei Branch, 6th Floor, 199, Tung-Hwa North Road, Taipei 105, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunn-Jy","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Dentistry and Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Chia","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Chang Gung Memorial Hospital, Taipei Branch, 6th Floor, 199, Tung-Hwa North Road, Taipei 105, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei-En","family":"Chang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Oral Biology, National Taiwan University Medical College, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Chia","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Cardinal Tien Hospital, New Taipei City 234, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Ling","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Chang Gung Memorial Hospital, Taipei Branch, 6th Floor, 199, Tung-Hwa North Road, Taipei 105, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hwa","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Chang Gung Memorial Hospital, Taipei Branch, 6th Floor, 199, Tung-Hwa North Road, Taipei 105, Taiwan"},{"name":"Graduate Department of Craniofacial Dentistry, Chang-Gung University Medical College, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiiang-Huei","family":"Jeng","sequence":"additional","affiliation":[{"name":"School of Dentistry and Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.2334\/josnusd.52.231","article-title":"Butyric acid stimulates bone sialoprotein gene transcription","volume":"52","author":"Yang","year":"2010","journal-title":"J. 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