{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:13:45Z","timestamp":1792030425839,"version":"4.4.0"},"reference-count":49,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the national research foundation of korea","award":["2018R1D1A1B07043282"],"award-info":[{"award-number":["2018R1D1A1B07043282"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Paeonia suffruticosa has been extensively used as a traditional medicine with various beneficial effects; paeonolide (PALI) was isolated from its dried roots. This study aimed to investigate the novel effects and mechanisms of PALI in pre-osteoblasts. Here, cell viability was evaluated using an MTT assay. Early and late osteoblast differentiation was examined by analyzing the activity of alkaline phosphatase (ALP) and by staining it with Alizarin red S (ARS). Cell migration was assessed using wound healing and Boyden chamber assays. Western blot and immunofluorescence analyses were used to examine the intracellular signaling pathways and differentiation proteins. PALI (0.1, 1, 10, 30, and 100 \u03bcM) showed no cytotoxic or proliferative effects in pre-osteoblasts. In the absence of cytotoxicity, PALI (1, 10, and 30 \u03bcM) promoted wound healing and transmigration during osteoblast differentiation. ALP staining demonstrated that PALI (1, 10, and 30 \u03bcM) promoted early osteoblast differentiation in a dose-dependent manner, and ARS staining showed an enhanced mineralized nodule formation, a key indicator of late osteoblast differentiation. Additionally, low concentrations of PALI (1 and 10 \u03bcM) increased the bone morphogenetic protein (BMP)\u2013Smad1\/5\/8 and Wnt\u2013\u03b2-catenin pathways in osteoblast differentiation. Particularly, PALI (1 and 10 \u03bcM) increased the phosphorylation of ERK1\/2 compared with BMP2 treatment, an FDA-approved drug for bone diseases. Furthermore, PALI-mediated early and late osteoblast differentiation was abolished in the presence of the ERK1\/2 inhibitor U0126. PALI-induced RUNX2 (Cbfa1) expression and nuclear localization were also attenuated by blocking the ERK1\/2 pathway during osteoblast differentiation. We suggest that PALI has biologically novel activities, such as enhanced osteoblast differentiation and bone mineralization mainly through the intracellular ERK1\/2-RUNX2 signaling pathway, suggesting that PALI might have therapeutic action and aid the treatment and prevention of bone diseases, such as osteoporosis and periodontitis.<\/jats:p>","DOI":"10.3390\/ijms22094924","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T11:10:27Z","timestamp":1620299427000},"page":"4924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Paeonolide as a Novel Regulator of Core-Binding Factor Subunit Alpha-1 in Bone-Forming Cells"],"prefix":"10.3390","volume":"22","author":[{"given":"Kyung-Ran","family":"Park","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon Yeop","family":"Lee","sequence":"additional","affiliation":[{"name":"National Institute for Korean Medicine Development, Gyeongsan 38540, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myounglae","family":"Cho","sequence":"additional","affiliation":[{"name":"National Institute for Korean Medicine Development, Gyeongsan 38540, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6534-9575","authenticated-orcid":false,"given":"Jin Tae","family":"Hong","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk 28160, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung-Mun","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,6]]},"reference":[{"key":"ref_1","first-page":"256","article-title":"Relationship between osteoporosis and periodontal disease: Review of the literature","volume":"9","author":"Esfahanian","year":"2012","journal-title":"J. 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