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Osthole-mediated cell differentiation through bone morphogenetic protein-2/p38 and extracellular signal-regulated kinase 1/2 pathway in human osteoblast cells.
J Pharmacol Exp Ther. 2005 Sep; 314(3):1290-9.JP

Abstract

The survival of osteoblast cells is one of the determinants of the development of osteoporosis in patients. Osthole (7-methoxy-8-isopentenoxycoumarin) is a coumarin derivative present in many medicinal plants. By means of alkaline phosphatase (ALP) activity, osteocalcin, osteopontin, and type I collagen, enzyme-linked immunosorbent assay, we have shown that osthole exhibits a significant induction of differentiation in two human osteoblast-like cell lines, MG-63 and hFOB. Induction of differentiation by osthole was associated with increased bone morphogenetic protein (BMP)-2 production and the activations of SMAD1/5/8 and p38 and extracellular signal-regulated kinase (ERK) 1/2 kinases. Addition of purified BMP-2 protein did not increase the up-regulation of ALP activity and osteocalcin by osthole, whereas the BMP-2 antagonist noggin blocked both osthole and BMP-2-mediated ALP activity enhancement, indicating that BMP-2 production is required in osthole-mediated osteoblast maturation. Pretreatment of osteoblast cells with noggin abrogated p38 activation but only partially decreased ERK1/2 activation, suggesting that BMP-2 signaling is required in p38 activation and is partially involved in ERK1/2 activation in osthole-treated osteoblast cells. Cotreatment of p38 inhibitor SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole] or p38 small interfering RNA (siRNA) expression inhibited osthole-mediated activation of ALP but only slightly affected osteocalcin production. In contrast, the production of osteocalcin induced by osthole was inhibited by the mitogen-activated protein kinase kinase inhibitor PD98059 (2'-amino-3'-methoxyflavone) or by expression of an ERK2 siRNA. These data suggest that BMP-2/p38 pathway links to the early phase, whereas ERK1/2 pathway is associated with the later phase in osthole-mediated differentiation of osteoblast cells. In this study, we demonstrate that osthole is a promising agent for treating osteoporosis.

Authors+Show Affiliations

Department of Biotechnology, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan. kuopolin@seed.net.twNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15956019

Citation

Kuo, Po-Lin, et al. "Osthole-mediated Cell Differentiation Through Bone Morphogenetic Protein-2/p38 and Extracellular Signal-regulated Kinase 1/2 Pathway in Human Osteoblast Cells." The Journal of Pharmacology and Experimental Therapeutics, vol. 314, no. 3, 2005, pp. 1290-9.
Kuo PL, Hsu YL, Chang CH, et al. Osthole-mediated cell differentiation through bone morphogenetic protein-2/p38 and extracellular signal-regulated kinase 1/2 pathway in human osteoblast cells. J Pharmacol Exp Ther. 2005;314(3):1290-9.
Kuo, P. L., Hsu, Y. L., Chang, C. H., & Chang, J. K. (2005). Osthole-mediated cell differentiation through bone morphogenetic protein-2/p38 and extracellular signal-regulated kinase 1/2 pathway in human osteoblast cells. The Journal of Pharmacology and Experimental Therapeutics, 314(3), 1290-9.
Kuo PL, et al. Osthole-mediated Cell Differentiation Through Bone Morphogenetic Protein-2/p38 and Extracellular Signal-regulated Kinase 1/2 Pathway in Human Osteoblast Cells. J Pharmacol Exp Ther. 2005;314(3):1290-9. PubMed PMID: 15956019.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Osthole-mediated cell differentiation through bone morphogenetic protein-2/p38 and extracellular signal-regulated kinase 1/2 pathway in human osteoblast cells. AU - Kuo,Po-Lin, AU - Hsu,Ya-Ling, AU - Chang,Cheng-Hsiung, AU - Chang,Jiunn-Kae, Y1 - 2005/06/13/ PY - 2005/6/16/pubmed PY - 2005/10/22/medline PY - 2005/6/16/entrez SP - 1290 EP - 9 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 314 IS - 3 N2 - The survival of osteoblast cells is one of the determinants of the development of osteoporosis in patients. Osthole (7-methoxy-8-isopentenoxycoumarin) is a coumarin derivative present in many medicinal plants. By means of alkaline phosphatase (ALP) activity, osteocalcin, osteopontin, and type I collagen, enzyme-linked immunosorbent assay, we have shown that osthole exhibits a significant induction of differentiation in two human osteoblast-like cell lines, MG-63 and hFOB. Induction of differentiation by osthole was associated with increased bone morphogenetic protein (BMP)-2 production and the activations of SMAD1/5/8 and p38 and extracellular signal-regulated kinase (ERK) 1/2 kinases. Addition of purified BMP-2 protein did not increase the up-regulation of ALP activity and osteocalcin by osthole, whereas the BMP-2 antagonist noggin blocked both osthole and BMP-2-mediated ALP activity enhancement, indicating that BMP-2 production is required in osthole-mediated osteoblast maturation. Pretreatment of osteoblast cells with noggin abrogated p38 activation but only partially decreased ERK1/2 activation, suggesting that BMP-2 signaling is required in p38 activation and is partially involved in ERK1/2 activation in osthole-treated osteoblast cells. Cotreatment of p38 inhibitor SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole] or p38 small interfering RNA (siRNA) expression inhibited osthole-mediated activation of ALP but only slightly affected osteocalcin production. In contrast, the production of osteocalcin induced by osthole was inhibited by the mitogen-activated protein kinase kinase inhibitor PD98059 (2'-amino-3'-methoxyflavone) or by expression of an ERK2 siRNA. These data suggest that BMP-2/p38 pathway links to the early phase, whereas ERK1/2 pathway is associated with the later phase in osthole-mediated differentiation of osteoblast cells. In this study, we demonstrate that osthole is a promising agent for treating osteoporosis. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/15956019/Osthole_mediated_cell_differentiation_through_bone_morphogenetic_protein_2/p38_and_extracellular_signal_regulated_kinase_1/2_pathway_in_human_osteoblast_cells_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15956019 DB - PRIME DP - Unbound Medicine ER -