Osthol, a Coumarin Isolated from Common Cnidium Fruit, Enhances the Differentiation and Maturation of Osteoblasts in vitro

Abstract

The effect of osthol on osteoblasts was investigated in primary osteoblastic cells isolated from newborn Wistar rats. Osthol was supplemented into cultured medium at 10^–7, 10^–6, 10^–5 and 10^–4 mol/l, respectively. No stimulating effect was found on cell proliferation, but 10^–5 mol/l osthol caused a significant increase in alkaline phosphatase (ALP) activity. Osteogenic differentiation markers were examined over a period of time at this concentration, and compared with control cells that were not supplemented with osthol. The results showed that the ALP activity, osteocalcin secretion and calcium deposition level in cells treated with osthol were 1.52, 2.74 and 2.0 times higher, respectively, than in the control cells. Results of ALP histochemical staining and mineralized bone nodule assays both showed that the number and area achieved in osthol-treated cells were 1.53-fold higher than in control cells. The gene expression of the growth and transcription factors basic fibroblast growth factor, insulin-like growth factor I, bone morphogenetic protein 2 (BMP-2), runt-related gene 2 (Runx-2) and osterix, which are associated with bone development, were also investigated. The increase in mRNA expression was 1.94, 1.74, 1.68, 1.83 and 2.31 times, respectively, higher compared to the control. Furthermore, osthol increased the protein expression of p38 mitogen-activated protein kinase (MAPK) and type I collagen. p38MAPK protein and collagen in osthol-treated cells were 1.42 and 1.58 times higher in osthol-treated cells compared to the control. The results of these studies support the conclusion that osthol significantly enhances the osteogenic differentiation of cultured osteoblasts. The results also indicated that osthol could stimulate the osteoblastic differentiation of rat calvarial osteoblast cultures by the BMP-2/p38MAPK/Runx-2/osterix pathway and that osthol may be used as an important compound in the development of new antiosteoporosis drugs.

Intermittent Stretching and Osteogenic Differentiation of Bone Marrow Derived Mesenchymal Stem Cells via the p38MAPK-Osterix Signaling Pathway

“…Specifically, the p38MAPK signaling pathway has a crucial role in the inflammatory response, regulating the cell cycle, cell differentiation and apoptosis [20,21]. Previous studies have shown that the p38MAPK signaling pathway has a close relationship with osteogenic differentiation of BMMSCs [2][3][4][5][6].…”

“…The p38MAPK signaling pathway plays a crucial role in the inflammatory reaction, regulation of the cell cycle, and cellular differentiation. Studies have demonstrated that the p38MAPK signaling pathway is related to osteogenic differentiation of BMMSCs [2][3][4][5][6]. Osterix is a recently discovered transcription factor related to bone formation as well as osteogenic differentiation.…”

The effect of the coumarin-like derivative osthole on the osteogenic properties of human periodontal ligament and jaw bone marrow mesenchymal stem cell sheets

“…Osthole exhibits estrogen-like effects, and in ovariectomized rats, it can prevent osteoporosis and reduce bone loss [42]. Although the cellular effects of osthole on osteoblast proliferation and differentiation have been documented [43,44], the value of osthole as an adjuvant for cell sheet formation remains to be determined. We hypothesized that osthole administration would facilitate cell sheet formation, increase cell matrix production, and positively influence the cellular behavior of the sheet-grafted cells in terms of differentiation and maturation, and hence enhance tissue regeneration and functional integration following in vivo transplantation.…”

N-Succinyl-chitosan nanoparticles coupled with low-density lipoprotein for targeted osthole-loaded delivery to low-density lipoprotein receptor-rich tumors

“…[5][6][7][8][9] Ost has various pharmacological and biological applications, and current research is focused on its antitumor activity. Several previous studies have reported that Ost is effective in inducing cell apoptosis, arresting cell cycle, and inhibiting cell proliferation.…”