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A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
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A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

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Trichostatin A-mediated upregulation of p21(WAF1) contributes to osteoclast apoptosis

TacGhee Yi1, Jeong-Hwa Baek, Hye-Jin Kim

  • 1Department of Cell and Developmental Biology, Dental Research Institute and BK21 Program, School of Dentistry, Seoul National University, Seoul 110-749, Korea.

Experimental & Molecular Medicine
|April 28, 2007
PubMed

Insights

Histone deacetylase inhibitors (HDIs) induce apoptosis in mature osteoclasts, partly via p21WAF1 upregulation. This finding supports HDIs as potential therapies for excessive bone resorption.

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Histone deacetylase inhibitors (HDIs) are emerging anti-cancer agents.
  • HDIs are known to inhibit osteoclast precursor formation and fusion.
  • The effects of HDIs on mature osteoclasts remain largely uncharacterized.

Purpose of the Study:

  • To investigate the impact of HDIs on mature osteoclasts.
  • To elucidate the mechanism underlying HDI-induced effects on osteoclasts.
  • To assess the therapeutic potential of HDIs for bone resorption disorders.

Main Methods:

  • Primary multinucleated mature osteoclasts were generated from mouse bone marrow.
  • Osteoclasts were treated with trichostatin A (TSA), a potent HDI.
  • Apoptosis was assessed via annexin V staining and caspase activation.
  • p21WAF1 expression was analyzed, and its role was investigated using shRNA-mediated knockdown.

Main Results:

  • TSA treatment induced apoptosis in mature osteoclasts.
  • TSA treatment led to the upregulation of p21WAF1 in osteoclasts.
  • Suppression of p21WAF1 attenuated TSA-induced osteoclast apoptosis.

Conclusions:

  • TSA induces apoptosis in mature osteoclasts through a mechanism involving p21WAF1 upregulation.
  • These findings highlight a novel action of HDIs on osteoclasts.
  • HDIs show promise as therapeutic agents for conditions characterized by excessive bone resorption.

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