Sesamin stimulates osteoblast differentiation through p38 and ERK1/2 MAPK signaling pathways

Abstract

BackgroundOsteoporosis is a worldwide health problem predominantly affecting post-menopausal women. Therapies aimed at increasing bone mass in osteoporetic patients lag behind comparable investigation of therapeutic strategies focusing on the bone resorption process. Sesamin, a major lignan compound found in Sesamun indicum Linn., has a variety of pharmacological effects, though its activity on bone cell function is unclear. Herein we examine the effect of this lignan on osteoblast differentiation and function.MethodCell cytotoxicity and proliferative in hFOB1.19 were examined by MTT and alamar blue assay up to 96 h of treatment. Gene expression of COL1, ALP, BMP-2, Runx2, OC, RANKL and OPG were detected after 24 h of sesamin treatment. ALP activity was measured at day 7, 14 and 21 of cultured. For mineralized assay, ADSCs were cultured in the presence of osteogenic media supplement with or without sesamin for 21 days and then stained with Alizarin Red S. MAPK signaling pathway activation was observed by using western blotting.ResultsSesamin promoted the gene expression of COL1, ALP, OCN, BMP-2 and Runx2 in hFOB1.19. On the other hand, sesamin was able to up-regulate OPG and down-regulate RANKL gene expression. ALP activity also significantly increased after sesamin treatment. Interestingly, sesamin induced formation of mineralized nodules in adipose derived stem cells (ADSCs) as observed by Alizarin Red S staining; this implies that sesamin has anabolic effects both on progenitor and committed cell stages of osteoblasts. Western blotting data showed that sesamin activated phosphorylation of p38 and ERK1/2 in hFOB1.19.ConclusionsThe data suggest that sesamin has the ability to trigger osteoblast differentiation by activation of the p38 and ERK MAPK signaling pathway and possibly indirectly regulate osteoclast development via the expression of OPG and RANKL in osteoblasts. Therefore, sesamin may be a promising phytochemical that could be developed for supplementation of osteoporotic therapy.

The Roles of Bone Morphogenetic Proteins and Their Signaling in the Osteogenesis of Adipose-Derived Stem Cells

“…79 Consistent with this finding, ERK is also important for the adipogenic and osteogenic commitment in ASCs. 68,[80][81][82][83] Inhibition of ERK by PD98059 blocks the expression of osteogenic differentiation-related proteins in a dose-dependent manner and switches ASCs to adipogenic differentiation. 83 Further, ERK is indispensable for the effects of sesamin, 81 akermanite, 68 wedelolactone, 82 and oncostatin M 80 in promoting the osteogenic differentiation and inhibiting adipogenic differentiation of ASCs.…”

“…96 Moreover, sesamin can stimulate the osteogenic differentiation of human ASCs with the upregulation of BMP-2, and further exert its effect via p38 and ERK1/2 MAPK signaling pathways. 68 …”

“…3 In ASCs, endogenous BMPs can also be induced by TGF-b1, 65 sonic hedgehog (shh), 66 inhibitor of b-catenin and TCF-4 (ICAT), 67 and sesamin. 68 These active agents may significantly contribute to a rapid significant progress of the ASC-based bone tissue engineering.…”

A Comprehensive Review on the Role of Various Materials in the Osteogenic Differentiation of Mesenchymal Stem Cells with a Special Focus on the Association of Heat Shock Proteins and Nanoparticles

“…It has been shown to enhance osteogenic differentiation in human fetal osteoblast 1 by upregulating osteoblast-related gene expression and ALP activity and also in adipose-derived stem cells via matrix mineralization [Wanachewin et al, 2012]. Osteogenesis has been stimulated via the p38 and ERK MAPK pathways.…”

An 8-O-4′ norlignan exerts oestrogen-like actions in osteoblastic cells via rapid nongenomic ER signaling pathway

“…Barks effectively suppressed the loss of bone induced by ovariectomy (OVX), and promoted primary osteoblastic cell proliferation, differentiation and osteoprotegrin (OPG) expression . Sesamin, the major lignan in sesame seeds, stimulated osteoblasts to mature and function by accelerating osteoblastogenic gene expression (Wanachewin et al, 2012). Lignans from the fruits and seeds of Schisandra chinensis (Turcz.)…”