ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2015
HDAC5 controls MEF2C-driven sclerostin expression in osteocytes.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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102 citing papers in PubMed, 156 citations in OpenAlex.
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- Fortilin binds and stabilizes MEF2C, activates it through phosphorylation, and drives transcription of the cell structural and survival protein CTNNA3.The Journal of biological chemistry · 2026Article
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- Fibroblast Growth Factor Receptor Signaling in Maturing Osteoblasts Controls Cell-Matrix Interactions Critical for Osteocyte Survival.bioRxiv : the preprint server for biology · 2026Article
- Cell signaling and transcriptional regulation of osteoclast lineage commitment, differentiation, bone resorption and diseases.Cell discovery · 2026Review
- Metformin attenuates diabetic osteoporosis via the miR-21 mediated Mef2c/Sost pathway.Frontiers in endocrinology · 2026Article
- Piezoelectric Biomaterials for Bone Regeneration: Roadmap from Dipole to Osteogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- A mouse model of Jansen's metaphyseal chondrodysplasia for investigating disease mechanisms and candidate therapeutics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Control of alveolar bone development, homeostasis, and socket healing by salt-inducible kinases.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- The Evolving Role of PTH Signaling in Osteocytes.Endocrinology · 2025Review
- Unlocking the Epigenetic Symphony: Histone Acetylation Orchestration in Bone Remodeling and Diseases.Stem cell reviews and reports · 2025Review
- OGT mediated HDAC5 O-GlcNAcylation promotes osteogenesis by regulating the homeostasis of epigenetic modifications and proteolysis.Journal of orthopaedic translation · 2025Article
- Nitric oxide contributes to rapid sclerostin protein loss following mechanical load.Biochemical and biophysical research communications · 2024Article
- Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis.Cell discovery · 2024Review
- Colchicine Blocks Abdominal Aortic Aneurysm Development by Maintaining Vascular Smooth Muscle Cell Homeostasis.International journal of biological sciences · 2024Article
- Osteocyte Mechanotransduction in Orthodontic Tooth Movement.Current osteoporosis reports · 2023Review
- Osteoblast-lineage calcium/calmodulin-dependent kinase 2 delta and gamma regulates bone mass and quality.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
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12 authors at 5 institutions in 1 country.
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Abstract
Osteocytes secrete paracrine factors that regulate the balance between bone formation and destruction. Among these molecules, sclerostin (encoded by the gene SOST) inhibits osteoblastic bone formation and is an osteoporosis drug target. The molecular mechanisms underlying SOST expression remain largely unexplored. Here, we report that histone deacetylase 5 (HDAC5) negatively regulates sclerostin levels in osteocytes in vitro and in vivo. HDAC5 shRNA increases, whereas HDAC5 overexpression decreases SOST expression in the novel murine Ocy454 osteocytic cell line. HDAC5 knockout mice show increased levels of SOST mRNA, more sclerostin-positive osteocytes, decreased Wnt activity, low trabecular bone density, and reduced bone formation by osteoblasts. In osteocytes, HDAC5 binds and inhibits the function of MEF2C, a crucial transcription factor for SOST expression. Using chromatin immunoprecipitation, we have mapped endogenous MEF2C binding in the SOST gene to a distal intergenic enhancer 45 kB downstream from the transcription start site. HDAC5 deficiency increases SOST enhancer MEF2C chromatin association and H3K27 acetylation and decreases recruitment of corepressors NCoR and HDAC3. HDAC5 associates with and regulates the transcriptional activity of this enhancer, suggesting direct regulation of SOST gene expression by HDAC5 in osteocytes. Finally, increased sclerostin production achieved by HDAC5 shRNA is abrogated by simultaneous knockdown of MEF2C, indicating that MEF2C is a major target of HDAC5 in osteocytes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.