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Article

Paeonolide as a Novel Regulator of Core-Binding Factor Subunit Alpha-1 in Bone-Forming Cells

1
Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul 02447, Korea
2
National Institute for Korean Medicine Development, Gyeongsan 38540, Korea
3
College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk 28160, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Maurizio Battino
Int. J. Mol. Sci. 2021, 22(9), 4924; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094924
Received: 17 March 2021 / Revised: 30 April 2021 / Accepted: 2 May 2021 / Published: 6 May 2021
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 μM) showed no cytotoxic or proliferative effects in pre-osteoblasts. In the absence of cytotoxicity, PALI (1, 10, and 30 μM) promoted wound healing and transmigration during osteoblast differentiation. ALP staining demonstrated that PALI (1, 10, and 30 μM) 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 μM) increased the bone morphogenetic protein (BMP)–Smad1/5/8 and Wnt–β-catenin pathways in osteoblast differentiation. Particularly, PALI (1 and 10 μM) 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. View Full-Text
Keywords: Paeonia suffruticosa; paeonolide; osteoblast differentiation; bone mineralization; ERK1/2; RUNX2; Cbfa1 Paeonia suffruticosa; paeonolide; osteoblast differentiation; bone mineralization; ERK1/2; RUNX2; Cbfa1
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MDPI and ACS Style

Park, K.-R.; Lee, J.Y.; Cho, M.; Hong, J.T.; Yun, H.-M. Paeonolide as a Novel Regulator of Core-Binding Factor Subunit Alpha-1 in Bone-Forming Cells. Int. J. Mol. Sci. 2021, 22, 4924. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094924

AMA Style

Park K-R, Lee JY, Cho M, Hong JT, Yun H-M. Paeonolide as a Novel Regulator of Core-Binding Factor Subunit Alpha-1 in Bone-Forming Cells. International Journal of Molecular Sciences. 2021; 22(9):4924. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094924

Chicago/Turabian Style

Park, Kyung-Ran, Joon Y. Lee, Myounglae Cho, Jin T. Hong, and Hyung-Mun Yun. 2021. "Paeonolide as a Novel Regulator of Core-Binding Factor Subunit Alpha-1 in Bone-Forming Cells" International Journal of Molecular Sciences 22, no. 9: 4924. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094924

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