Transcription Factor Hematopoietically Expressed Homeobox Protein (Hhex) Negatively Regulates Osteoclast Differentiation by Controlling Cyclin‐Dependent Kinase Inhibitors
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- Hisato Watanabe
- Department of Orthopaedic Surgery, Faculty of Medicine The University of Tokyo Tokyo Japan
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- Hiroyuki Okada
- Center for Disease Biology and Integrative Medicine, Graduate School of Medicine The University of Tokyo Tokyo Japan
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- Jun Hirose
- Department of Orthopaedic Surgery, Faculty of Medicine The University of Tokyo Tokyo Japan
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- Yasunori Omata
- Department of Orthopaedic Surgery, Faculty of Medicine The University of Tokyo Tokyo Japan
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- Takumi Matsumoto
- Department of Orthopaedic Surgery, Faculty of Medicine The University of Tokyo Tokyo Japan
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- Morio Matsumoto
- Department of Orthopaedic Surgery Keio University School of Medicine Tokyo Japan
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- Masaya Nakamura
- Department of Orthopaedic Surgery Keio University School of Medicine Tokyo Japan
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- Taku Saito
- Department of Orthopaedic Surgery, Faculty of Medicine The University of Tokyo Tokyo Japan
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- Takeshi Miyamoto
- Department of Orthopedic Surgery Kumamoto University Kumamoto Japan
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- Sakae Tanaka
- Department of Orthopaedic Surgery, Faculty of Medicine The University of Tokyo Tokyo Japan
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説明
<jats:title>ABSTRACT</jats:title><jats:p>We investigated the role of hematopoietically expressed homeobox protein (Hhex) in osteoclast development. Trimethylation of lysine 27 of histone H3 at the <jats:italic>cis</jats:italic>‐regulatory element of <jats:italic>Hhex</jats:italic> was maintained and that of lysine 4 was reduced during receptor activator of nuclear factor κB ligand (RANKL)‐induced osteoclastogenesis, which was associated with a reduction of <jats:italic>Hhex</jats:italic> expression. Overexpression of <jats:italic>Hhex</jats:italic> in bone marrow–derived macrophages inhibited, whereas <jats:italic>Hhex</jats:italic> suppression promoted, RANKL‐induced osteoclastogenesis in vitro. Conditional deletion of <jats:italic>Hhex</jats:italic> in osteoclast‐lineage cells promoted osteoclastogenesis and reduced cancellous bone volume in mice, confirming the negative regulatory role of Hhex in osteoclast differentiation. Expression of cyclin‐dependent kinase inhibitors such as Cdkn2a and Cdkn1b in osteoclast precursors was negatively regulated by Hhex, and <jats:italic>Hhex</jats:italic> deletion increased the ratio of cells at the G1 phase of the cell cycle. In conclusion, Hhex is an inhibitor of osteoclast differentiation that is regulated in an epigenetic manner and regulates the cell cycle of osteoclast precursors and the skeletal homeostasis. © 2022 The Authors. <jats:italic>JBMR Plus</jats:italic> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.</jats:p>
収録刊行物
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- JBMR Plus
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JBMR Plus 6 (4), 2022-02-14
Oxford University Press (OUP)
