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Updated: Apr 5, 2026
14:32
Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates
Published on: February 27, 2016
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Sirtuin1 Suppresses Osteoclastogenesis by Deacetylating FoxOs
Ha-Neui Kim1, Li Han1, Srividhya Iyer1
1Division of Endocrinology and Metabolism (H.-N.K., L.H., S.I., H.Z., C.A.O., S.C.M., M.A.), Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205; and Translational Gerontology Branch (R.d.C.), National Institute on Aging, Baltimore, Maryland 21224.
Molecular Endocrinology (Baltimore, Md.)
|August 20, 2015
Summary
Sirtuin1 (Sirt1) activation reduces bone loss by inhibiting osteoclast formation through forkhead box (Fox) proteins. This pathway impairs mitochondria, offering a dual approach to combat osteoporosis.
Area of Science:
- Molecular Biology
- Bone Biology
- Metabolism
Background:
- Sirtuin1 (Sirt1) activation by compounds like resveratrol attenuates bone loss.
- Sirt1 plays a role in regulating osteoclast activity and bone resorption.
- Forkhead box (Fox) proteins are known targets of Sirt1 and influence cellular processes.
Purpose of the Study:
- To investigate if Sirt1's anti-resorptive effects on bone are mediated by FoxO proteins.
- To elucidate the molecular mechanisms linking Sirt1, FoxOs, and osteoclastogenesis.
Main Methods:
- Treatment of murine osteoclast progenitors with Sirt1 activators (SRT2104, SRT3025).
- Assessment of osteoclast progenitor proliferation and osteoclastogenesis.
- Analysis of FoxO protein acetylation and transcriptional activity.
- Measurement of target gene expression (catalase, hemeoxygenase-1) and cellular ATP levels.
Main Results:
- Sirt1 activation inhibited osteoclast progenitor proliferation and osteoclastogenesis.
- These effects were dependent on the presence of FoxO1, FoxO3, and FoxO4.
- Sirt1 activators decreased ATP production in osteoclast progenitors via FoxOs, linked to reduced mitochondrial activity.
- FoxO-mediated transcription of genes like hemeoxygenase-1 was modulated by Sirt1.
Conclusions:
- The anti-osteoclastogenic effects of Sirt1 are mediated through deacetylation and activation of FoxO proteins.
- Impaired mitochondrial activity and reduced ATP production in osteoclasts are key mechanisms.
- Sirt1 activators demonstrate dual efficacy against osteoporosis by inhibiting bone resorption and promoting bone formation via FoxOs.
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