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Related Concept Videos

Adrenergic Antagonists: Chemistry and Classification of ɑ-Receptor Blockers01:17

Adrenergic Antagonists: Chemistry and Classification of ɑ-Receptor Blockers

Adrenergic antagonists, or sympatholytics, inhibit adrenoceptor activation driven by catecholamines or agonists. Based on their adrenoceptor specificity, adrenergic blockers can be categorized into two primary groups: α-adrenergic blockers (α-blockers) and β-adrenergic blockers (β-blockers). α-blockers interact with α1 and α2 subtypes of α-adrenoceptors.
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Isolation and Enrichment of Human Adipose-derived Stromal Cells for Enhanced Osteogenesis
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Published on: January 12, 2015

Alpha-adrenergic blocker mediated osteoblastic stem cell differentiation.

Yoon Jung Choi1, Jue Yeon Lee, Seung Jin Lee

  • 1Craniomaxillofacial Reconstructive Sciences Major, College of Dentistry, Seoul National University, Seoul 110-749, South Korea.

Biochemical and Biophysical Research Communications
|October 18, 2011
PubMed
Summary

Doxazosin, an alpha-blocker, promotes osteogenic stem cell differentiation by activating ERK1/2 signaling. This finding supports the protective effects of antihypertensive drugs against bone loss and fracture risk.

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Published on: May 4, 2018

Area of Science:

  • Bone Metabolism
  • Stem Cell Differentiation
  • Pharmacology

Background:

  • Antihypertensive drugs, including alpha- or beta-blockers, may prevent bone loss and reduce fracture risk.
  • Limited information exists regarding the mechanisms of action of these drugs on bone health.

Purpose of the Study:

  • To investigate the effects of doxazosin, an alpha-blocker used for benign prostatic hyperplasia (BPH), on osteogenic stem cell differentiation.
  • To elucidate the underlying molecular mechanisms, particularly the role of ERK1/2 signaling.

Main Methods:

  • Human mesenchymal stem cells were treated with doxazosin.
  • Osteogenic differentiation was assessed using Alizarin red S staining and calcein.
  • Gene and protein expression of osteogenic markers and ERK1/2 phosphorylation were analyzed.
  • MAP kinase inhibitor (U0126) was used to block signaling pathways.

Main Results:

  • Doxazosin significantly increased osteogenic differentiation of human mesenchymal stem cells.
  • Doxazosin upregulated key osteogenic markers (alkaline phosphatase, type I collagen, osteopontin, osteocalcin).
  • Doxazosin enhanced ERK1/2 phosphorylation, which was crucial for its osteogenic effects as U0126 blocked the differentiation.

Conclusions:

  • Doxazosin promotes osteogenic differentiation of adult stem cells through ERK1/2 activation.
  • These findings suggest a potential therapeutic role for doxazosin in bone metabolism and fracture risk reduction.
  • Doxazosin may contribute to the protective effects of antihypertensive medications on bone health.