Oncotarget

Research Papers: Pathology:

Sulfuretin promotes osteoblastic differentiation in primary cultured osteoblasts and in vivo bone healing

Q-Schick Auh, Kyung-Ran Park, Hyung-Mun Yun, Hyun-Chang Lim, Ga-Hyun Kim, Dong-Sung Lee, Youn-Chul Kim, Hyuncheol Oh and Eun-Cheol Kim _

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Oncotarget. 2016; 7:78320-78330. https://doi.org/10.18632/oncotarget.12460

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Abstract

Q-Schick Auh1,*, Kyung-Ran Park2,*, Hyung-Mun Yun3, Hyun-Chang Lim 4, Ga-Hyun Kim2, Dong-Sung Lee5, Youn-Chul Kim6, Hyuncheol Oh6 and Eun-Cheol Kim3

1 Department of Oral Medicine, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea

2 Department of Oral & Maxillofacial Regeneration, Graduate School, Kyung Hee University, Seoul, Republic of Korea

3 Department of Oral and Maxillofacial Pathology, School of Dentistry and Research Center for Tooth & Periodontal Regeneration (MRC), Kyung Hee University, Seoul, Republic of Korea

4 Department of Periodontology, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea

5 Department of Biomedical Chemistry, College of Health and Biomedical Science, Konkuk University, Chung-Ju, Republic of Korea

6 Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan, Republic of Korea

* These authors have contributed equally to this manuscript

Correspondence to:

Eun-Cheol Kim, email:

Keywords: Osteoblasts; Differentiation; In vitro; In vivo; Osteogenesis; Signal pathways, Pathology Section

Received: March 15, 2016 Accepted: September 13, 2016 Published: October 04, 2016

Abstract

Although sulfuretin, the major flavonoid of Rhus verniciflua Stokes, has a variety of biological actions, its in vitro and in vivo effects on osteogenic potential remain poorly understood. The objective of the present study was to investigate the effects of sulfuretin on in vitro osteoblastic differentiation and the underlying signal pathway mechanisms in primary cultured osteoblasts and on in vivo bone formation using critical-sized calvarial defects in mice. Sulfuretin promoted osteogenic differentiation of primary osteoblasts, with increased ALP activity and mineralization, and upregulated differentiation markers, including ALP, osteocalcin, and osteopontin, in a concentration-dependent manner. The expression levels of Runx2, BMP-2, and phospho-Smad1/5/8 were upregulated by sulfuretin. Moreover, sulfuretin increased phosphorylation of Akt, mTOR, ERK, and JNK. Furthermore, sulfuretin treatment increased mRNA expression of Wnt ligands, phosphorylation of GSK3, and nuclear β-catenin protein expression. In vivo studies with calvarial bone defects revealed that sulfuretin significantly enhanced new bone formation by micro-computed tomography and histologic analysis. Collectively, these data suggest that sulfuretin acts through the activation of BMP, mTOR, Wnt/β-catenin, and Runx2 signaling to promote in vitro osteoblast differentiation and facilitate in vivo bone regeneration, and might be have therapeutic benefits in bone disease and regeneration.


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