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Updated: May 16, 2026

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
Published on: March 15, 2018
HDAC7 inhibits osteoclastogenesis by reversing RANKL-triggered β-catenin switch
Zixue Jin1, Wei Wei, Paul C Dechow
1Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Abstract:
The bone-resorbing osteoclast is essential for skeletal remodeling, yet its deregulation contributes to diseases such as osteoporosis and cancer bone metastasis. Here we identify histone deacetylase 7 (HDAC7) as a key negative regulator of osteoclastogenesis and bone resorption using both in vitro cellular and molecular analyses and in vivo characterization of conditional HDAC7-knockout mice. Bone marrow osteoclast differentiation assays reveal that HDAC7 overexpression suppresses, whereas HDAC7 deletion enhances, osteoclastogenesis. Mechanistically, in the absence of receptor activator of nuclear factor κ-B ligand (RANKL), HDAC7 attenuates β-catenin function and cyclin D1 expression, thereby reducing precursor proliferation; upon RANKL activation, HDAC7 suppresses NFATc1 and prevents β-catenin down-regulation, thereby blocking osteoclast differentiation. Consequently, HDAC7 deletion in the osteoclast lineage results in a 26% reduction in bone mass (P = 0.003) owing to 102% elevated bone resorption (P = 0.01). These findings are clinically significant in light of the remarkable therapeutic potentials of HDAC inhibitors for several diseases such as cancer, diabetes, and neurodegeneration.
Insights
Histone deacetylase 7 (HDAC7) negatively regulates osteoclast formation and bone resorption. Its absence increases bone breakdown, offering therapeutic potential for bone diseases.
Area of Science:
- Cell Biology
- Molecular Biology
- Bone Biology
Background:
- Osteoclasts are crucial for bone remodeling, but their dysregulation causes diseases like osteoporosis and bone metastasis.
- Histone deacetylase 7 (HDAC7) has emerged as a potential factor in cellular processes.
Purpose of the Study:
- To investigate the role of HDAC7 in osteoclastogenesis and bone resorption.
- To elucidate the molecular mechanisms by which HDAC7 regulates osteoclast formation.
Main Methods:
- In vitro cellular and molecular analyses of osteoclast differentiation.
- In vivo characterization of conditional HDAC7-knockout mice.
- Bone marrow osteoclast differentiation assays.
Main Results:
- HDAC7 overexpression suppressed osteoclastogenesis, while HDAC7 deletion enhanced it.
- HDAC7 regulated β-catenin and cyclin D1 expression, impacting precursor proliferation.
- Upon RANKL activation, HDAC7 modulated NFATc1 and β-catenin, affecting osteoclast differentiation.
- HDAC7 deletion in osteoclasts led to reduced bone mass and increased bone resorption.
Conclusions:
- HDAC7 is a key negative regulator of osteoclastogenesis and bone resorption.
- Targeting HDAC7 may offer therapeutic strategies for bone-related diseases.
- The findings highlight the clinical significance of HDAC inhibitors for various conditions.
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