title: Kirenol stimulates osteoblast differentiation through activation of the BMP and Wnt/β-catenin signaling pathways in MC3T3-E1 cells.
abstract: Kirenol has been reported to possess anti-oxidant, anti-inflammatory, anti-allergic, anti-adipogenic, and anti-arthritic activities; however, its effect on osteoblast differentiation has not yet been reported. The aim of the present study was to evaluate the effect of kirenol on osteoblast differentiation through activation of the bone morphogenetic protein (BMP) and Wnt/β-catenin signaling pathways in MC3T3-E1 cells. Kirenol markedly promoted alkaline phosphatase (ALP) activity and mineralization. Kirenol not only increased the expression of osteoblast differentiation markers, such as ALP, type I collagen (ColA1), and osteopontin (OPN), but also increased the expression of osteoprotegerin/receptor activator of nuclear factor kappa B ligand (OPG/RANKL) ratio. The effects of kirenol on osteoblast differentiation were accompanied by stimulating the expression of the BMP and Wnt/β-catenin signaling pathways, including BMP2, runt-related transcription factor 2 (Runx2), osterix (Osx), low density lipoprotein receptor related protein 5 (LRP5), disheveled 2 (DVL2), β-catenin, cyclin D1 (CCND1), and phosphorylated glycogen synthase kinase 3β (GSK3β). In addition, kirenol up-regulated the expression of β-catenin, CCND1, ALP, and ColA1 which were down-regulated by siRNA knockdown of β-catenin. Overall, these results demonstrate that kirenol is capable of promoting osteoblast differentiation in MC3T3-E1 cells through activation of the BMP and Wnt/β-catenin signaling pathways, suggesting that it is a potential candidate target for treating or preventing osteoporosis.
authors: Department of Biomaterials Science and Engineering, Yonsei University, Seoul 120-749, Republic of Korea.
authors: Mi-Bo
authors: MB
authors: Kim
authors: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors: Youngwoo
authors: Y
authors: Song
authors: Department of Biomaterials Science and Engineering, Yonsei University, Seoul 120-749, Republic of Korea; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea. Electronic address: jkhwang@yonsei.ac.kr.
authors: Jae-Kwan
authors: JK
authors: Hwang
mesh_terms: D016475:3T3 Cells; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D004224:Diterpenes / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics
chemical_list: D019485:Bone Morphogenetic Proteins; C495267:CTNNB1 protein, mouse; D004224:Diterpenes; D051176:beta Catenin; C560087:kirenol
keywords: BMP; Kirenol; Osteoblast differentiation; Wnt/β-catenin