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<p>Osteoclasts are specialized cells essential for bone resorption, a crucial process in bone remodeling, and dysregulation of osteoclastogenesis can lead to pathological bone loss such as osteoporosis and rheumatoid arthritis. Therefore, understanding the precise mechanisms governing osteoclast differentiation is crucial for developing effective therapies for skeletal diseases. In osteoclastogenesis, as well as other differentiated cells, it is well understood that cell cycle arrest is essential for terminal differentiation and is tightly regulated by CDK inhibitors such as Cip/Kip family and Ink4 family protein. In this manuscript, we identified p15<sup>Ink4b</sup>, a member of the Ink4 family, as a novel regulator of osteoclastogenesis by comprehensive single-cell RNA sequence data reanalyzing. Furthermore, histological analysis and in vitro osteoclast differentiation assay revealed that p15<sup>Ink4b</sup> functionally regulates osteoclastogenesis. Our findings may not only provide insights into the molecular mechanisms of osteoclast differentiation but also underscore the potential of harnessing cell cycle mechanisms to develop novel therapeutic strategies for bone diseases.</p>

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Cell cycle checkpoint factor p15Ink4b is a novel regulator of osteoclast differentiation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月20日

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  • Shunya Tsuji,
  • Sora Mizukami,
  • Akihiko Sakamoto,
  • Kenji Takemoto,
  • Tetsuya Seto,
  • Kazuya Uehara,
  • Kiminori Yukata,
  • Takashi Sakai,
  • Keiko Iwaisako,
  • Norihiko Takeda,
  • Ryoji Yanai,
  • Masataka Asagiri

摘要

Osteoclasts are specialized cells essential for bone resorption, a crucial process in bone remodeling, and dysregulation of osteoclastogenesis can lead to pathological bone loss such as osteoporosis and rheumatoid arthritis. Therefore, understanding the precise mechanisms governing osteoclast differentiation is crucial for developing effective therapies for skeletal diseases. In osteoclastogenesis, as well as other differentiated cells, it is well understood that cell cycle arrest is essential for terminal differentiation and is tightly regulated by CDK inhibitors such as Cip/Kip family and Ink4 family protein. In this manuscript, we identified p15Ink4b, a member of the Ink4 family, as a novel regulator of osteoclastogenesis by comprehensive single-cell RNA sequence data reanalyzing. Furthermore, histological analysis and in vitro osteoclast differentiation assay revealed that p15Ink4b functionally regulates osteoclastogenesis. Our findings may not only provide insights into the molecular mechanisms of osteoclast differentiation but also underscore the potential of harnessing cell cycle mechanisms to develop novel therapeutic strategies for bone diseases.