ArticleThe Journal of biological chemistry2014
Class I and IIa histone deacetylases have opposite effects on sclerostin gene regulation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Changes in bone mineral density in Down syndrome individuals: a systematic review and meta-analysis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2022Pooled it
- Focal Adhesion Kinase Promotes Calcification of Vascular Smooth Muscle Cells via Regulation of Histone Deacetylase 4 and 5.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Direct and indirect effects of transforming growth factor-beta on osteoclast-mediated bone remodeling using a new in vitro bone matrix model.JBMR plus · 2025Article
- Unlocking the Epigenetic Symphony: Histone Acetylation Orchestration in Bone Remodeling and Diseases.Stem cell reviews and reports · 2025Review
- Norepinephrine, beyond the Synapse: Coordinating Epigenetic Codes for Memory.International journal of molecular sciences · 2022Review
- Positive and Negative Regulators of Sclerostin Expression.International journal of molecular sciences · 2022Review
- Role of histone modification in the occurrence and development of osteoporosis.Frontiers in endocrinology · 2022Review
- Article
- METTL3 induces bone marrow mesenchymal stem cells osteogenic differentiation and migration through facilitating M1 macrophage differentiation.American journal of translational research · 2021Article
- The Mechanosensory Role of Osteocytes and Implications for Bone Health and Disease States.Frontiers in cell and developmental biology · 2021Review
- The Regulation of Bone Metabolism and Disorders by Wnt Signaling.International journal of molecular sciences · 2019Review
- Regulation of Osteoclast Differentiation and Skeletal Maintenance by Histone Deacetylases.Molecules (Basel, Switzerland) · 2019Review
- The Bromodomain InhibitorInternational journal of molecular sciences · 2018Article
- Postnatal deletion of β-catenin in osterix-expressing cells is necessary for bone growth and intermittent PTH-induced bone gain.Journal of bone and mineral metabolism · 2018Article
- Regulation of Bone Remodeling by Parathyroid Hormone.Cold Spring Harbor perspectives in medicine · 2018Review
- The Deletion of Hdac4 in Mouse Osteoblasts Influences Both Catabolic and Anabolic Effects in Bone.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2018Article
- Parathyroid Hormone Signaling in Osteocytes.JBMR plus · 2018Review
- MEF2C Interacts With c-FOS in PTH-Stimulated Mmp13 Gene Expression in Osteoblastic Cells.Endocrinology · 2017Article
- Article
- Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adult bone mass is controlled by the bone formation repressor sclerostin (SOST). Previously, we have shown that intermittent parathyroid hormone (PTH) bone anabolic therapy involves SOST expression reduction by inhibiting myocyte enhancer factor 2 (MEF2), which activates a distant bone enhancer. Here, we extended our SOST gene regulation studies by analyzing a role of class I and IIa histone deacetylases (HDACs), which are known regulators of MEF2s. Expression analysis using quantitative PCR (qPCR) showed high expression of HDACs 1 and 2, lower amounts of HDACs 3, 5, and 7, low amounts of HDAC4, and no expression of HDACs 8 and 9 in constitutively SOST-expressing UMR106 osteocytic cells. PTH-induced Sost suppression was associated with specific rapid nuclear accumulation of HDAC5 and co-localization with MEF2s in nuclear speckles requiring serine residues 259 and 498, whose phosphorylations control nucleocytoplasmic shuttling. Increasing nuclear levels of HDAC5 in UMR106 by blocking nuclear export with leptomycin B (LepB) or overexpression in transient transfection assays inhibited endogenous Sost transcription and reporter gene expression, respectively. This repressor effect of HDAC5 did not require catalytic activity using specific HDAC inhibitors. In contrast, inhibition of class I HDAC activities and expression using RNA interference suppressed constitutive Sost expression in UMR106 cells. An unbiased comprehensive search for involved HDAC targets using an acetylome analysis revealed several non-histone proteins as candidates. These findings suggest that PTH-mediated Sost repression involves nuclear accumulation of HDAC inhibiting the MEF2-dependent Sost bone enhancer, and class I HDACs are required for constitutive Sost expression in osteocytes.
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Registered trials
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.