Effects of the 1, 4-dihydropyridine L-type calcium channel blocker benidipine on bone marrow stromal cells.
Osteoporosis (OP) often increases the risk of bone fracture and other complications and is a major clinical problem. Previous studies have found that high blood pressure is associated with bone formation abnormalities, resulting in increased calcium loss. We have investigated the effect of the antihypertensive drug benidipine on bone marrow stromal cell (BMSC) differentiation into osteoblasts and bone formation under osteoporotic conditions. We used a combination of in vitro and in vivo approaches to test the hypothesis that benidipine promotes murine BMSC differentiation into osteoblasts. Alkaline phosphatase (ALP), osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), β-catenin, and low-density lipoprotein receptor-related protein 5 (LRP5) protein expression was evaluated in primary femoral BMSCs from C57/BL6 mice cultured under osteogenic conditions for 2 weeks to examine the effects of benidipine. An ovariectomized (OVX) mouse model was used to investigate the effect of benidipine treatment for 3 months in vivo. We found that ALP, OCN, and RUNX2 expression was up-regulated and WNT/β-catenin signaling was enhanced in vitro and in vivo. In OVX mice that were intragastrically administered benidipine, bone parameters (trabecular thickness, bone mineral density, and trabecular number) in the distal femoral metaphysis were significantly increased compared with control OVX mice. Consistently, benidipine promoted BMSC differentiation into osteoblasts and protected against bone loss in OVX mice. Therefore, benidipine might be a suitable candidate for the treatment of patients with postmenopausal osteoporosis and hypertension.
Department of Orthopedics, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Road, Guangzhou, Guangdong, 510630, People's Republic of China.
Zhong-ping
ZP
Ma
Jia-cheng
JC
Liao
Chang
C
Zhao
Dao-zhang
DZ
Cai
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000032:analysis; D004095:Dihydropyridines / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects; D015675:Osteocalcin / Q000032:analysis; D010012:Osteogenesis / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D060449:Wnt Signaling Pathway / Q000187:drug effects
D002121:Calcium Channel Blockers; D050659:Core Binding Factor Alpha 1 Subunit; D004095:Dihydropyridines; C493716:Runx2 protein, mouse; D014665:Vasodilator Agents; D015675:Osteocalcin; C061004:benidipine