Fasudil hydrochloride induces osteoblastic differentiation of stromal cell lines, C3H10T1/2 and ST2, via bone morphogenetic protein-2 expression.
Rho-kinase (ROK), downstream of the mevalonate pathway, is detrimental to vessels, and suppressing its activity is a target for the treatment of human disease such as coronary artery disease and pulmonary hypertension. Recent studies have shown that ROK has a crucial role in bone metabolism. However, the role of ROK in stromal cells is still unclear. The present study was undertaken to investigate the effect of a ROK inhibitor, fasudil hydrochloride, on stromal cell lines, C3H10T1/2 and ST2. In both cells, Fasudil significantly stimulated alkaline phosphatase activity and enhanced cell mineralization. Moreover, fasudil significantly increased the mRNA expression of collagen-I, osteocalcin, and bone morphogenetic protein-2 (BMP-2). Supplementation of noggin, a BMP-2 antagonist, significantly reversed the fasudil-induced collagen-I and osteocalcin mRNA expression in both cells. These findings suggest that fasudil induces the osteoblastic differentiation of stromal cells via enhancing BMP-2 expression, and that this drug might be beneficial for not only atherosclerosis but also osteoporosis by promoting bone formation.
Kanazawa
Ippei
I
Department of Internal Medicine 1, Shimane University Faculty of Medicine, Izumo, Japan. ippei.k@med.shimane-u.ac.jp
Yamaguchi
Toru
T
Yano
Shozo
S
Yamauchi
Mika
M
Sugimoto
Toshitsugu
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002113:Calcification, Physiologic / Q000187:drug effects / Q000235:genetics; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism; D000099176:Noggin Protein
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D055396:Bone Morphogenetic Protein 2; D002352:Carrier Proteins; D047428:Protein Kinase Inhibitors; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C049347:fasudil