Alpha-adrenergic blocker mediated osteoblastic stem cell differentiation

Yoon Jung Choi; Jue Yeon Lee; Seung Jin Lee; Chong Pyoung Chung; Yoon Jeong Park

doi:10.1016/j.bbrc.2011.09.095

Alpha-adrenergic blocker mediated osteoblastic stem cell differentiation

Yoon Jung Choi, Jue Yeon Lee, Seung Jin Lee, Chong Pyoung Chung, Yoon Jeong Park

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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.

Original language	English
Pages (from-to)	232-238
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	416
Issue number	3-4
DOIs	https://doi.org/10.1016/j.bbrc.2011.09.095
State	Published - 16 Dec 2011

Bibliographical note

Funding Information:
This study was supported in part by the Korean Science and Technology Foundation (KOSEF) Nanobiotechnology Development Program and in part by Engineering Research Center grant from KOSEF through the Intelligent Biointerface Engineering Center (IBEC), Seoul National University, Korea.

Keywords

Alpha-blocker
Doxazosin
Extracellular signal-regulated kinase (ERK)
Human mesenchymal stem cells
Osteogenic differentiation

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10.1016/j.bbrc.2011.09.095

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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.",

keywords = "Alpha-blocker, Doxazosin, Extracellular signal-regulated kinase (ERK), Human mesenchymal stem cells, Osteogenic differentiation",

author = "Choi, {Yoon Jung} and Lee, {Jue Yeon} and Lee, {Seung Jin} and Chung, {Chong Pyoung} and Park, {Yoon Jeong}",

note = "Funding Information: This study was supported in part by the Korean Science and Technology Foundation (KOSEF) Nanobiotechnology Development Program and in part by Engineering Research Center grant from KOSEF through the Intelligent Biointerface Engineering Center (IBEC), Seoul National University, Korea. ",

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IS - 3-4

ER -

Alpha-adrenergic blocker mediated osteoblastic stem cell differentiation

Abstract

Bibliographical note

Keywords

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