title: Alpha-adrenergic blocker mediated osteoblastic stem cell differentiation.
abstract: Recent researches have indicated a role for antihypertensive drugs including alpha- or beta-blockers in the prevention of bone loss. Some epidemiological studies reported the protective effects of those agents on fracture risk. However, there is limited information on the association with those agents especially at the mechanism of action. In the present study, we investigated the effects of doxazosin, an alpha-blocker that is clinically used for the treatment of benign prostatic hyperplasia (BPH) along with antihypertensive medication, on the osteogenic stem cell differentiation. We found that doxazosin increased osteogenic differentiation of human mesenchymal stem cells, detected by Alizarin red S staining and calcein. Doxazosin not only induced expression of alkaline phosphatase, type I collagen, osteopontin, and osteocalcin, it also resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK1/2), a MAP kinase involved in osteoblastic differentiation. Treatment with U0126, a MAP kinase inhibitor, significantly blocked doxazosin-induced osteoblastic differentiation. Unrelated to activation of osteogenic differentiation by doxazosin, we found that there were no significant changes in adipogenic differentiation or in the expression of adipose-specific genes, including peroxisome proliferator-activated receptor γ, aP2, or LPL. In this report, we suggest that doxazosin has the ability to increase osteogenic cell differentiation via ERK1/2 activation in osteogenic differentiation of adult stem cells, which supports the protective effects of antihypertensive drug on fracture risk and according to our data doxazosin might be useful for application in the field of bone metabolism.
authors: Craniomaxillofacial Reconstructive Sciences Major, College of Dentistry, Seoul National University, Seoul 110-749, South Korea.
authors: Yoon Jung
authors: YJ
authors: Choi
authors: Jue Yeon
authors: JY
authors: Lee
authors: Seung Jin
authors: SJ
authors: Lee
authors: Chong-Pyoung
authors: CP
authors: Chung
authors: Yoon Jeong
authors: YJ
authors: Park
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D017292:Doxazosin / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D017292:Doxazosin