Ninjurin1 positively regulates osteoclast development by enhancing the survival of prefusion osteoclasts
- 주제(기타) Biochemistry & Molecular Biology; Medicine, Research & Experimental
- 설명문(일반) [Bae, Sung-Jin; Shin, Min Wook; Son, Taekwon; Lee, Hye Shin; Kim, Kyu-Won] Seoul Natl Univ, Coll Pharm, Seoul 08826, South Korea; [Bae, Sung-Jin; Shin, Min Wook; Son, Taekwon; Lee, Hye Shin; Kim, Kyu-Won] Seoul Natl Univ, Res Inst Pharmaceut Sci, Seoul 08826, South Korea; [Chae, Ji Soo] PerkinElmer, Dept Life Sci & Technol, Seoul 06702, South Korea; [Jeon, Sejin; Oh, Goo Taeg] Ewha Womans Univ, Dept Life Sci, Seoul 03760, South Korea; [Kim, Kyu-Won] Seoul Natl Univ, Crop Biotechnol Inst, GreenBio Sci & Technol, Pyeongchang 25354, South Korea; [Bae, Sung-Jin] Pusan Natl Univ, Korean Med Res Ctr Hlth Aging, Yangsan 50612, South Korea; [Shin, Min Wook] Univ Massachusetts, RNA Therapeut Inst, Med Sch, Worcester, MA 01605 USA
- OA유형 Green Published, gold
- 발행기관 NATURE PUBLISHING GROUP
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000159978
- 본문언어 영어
- Published As http://dx.doi.org/10.1038/s12276-018-0201-3
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Osteoclasts (OCs) are bone-resorbing cells that originate from hematopoietic stem cells and develop through the fusion of mononuclear myeloid precursors. Dysregulation of OC development causes bone disorders such as osteopetrosis, osteoporosis, and rheumatoid arthritis. Although the molecular mechanisms underlying osteoclastogenesis have been well established, the means by which OCs maintain their survival during OC development remain unknown. We found that Ninjurin1 (Ninj1) expression is dynamically regulated during osteoclastogenesis and that Ninj1(-/-) mice exhibit increased trabecular bone volume owing to impaired OC development. Ninj1 deficiency did not alter OC differentiation, transmigration, fusion, or actin ring formation but increased Caspase-9-dependent intrinsic apoptosis in prefusion OCs (preOCs). Overexpression of Ninj1 enhanced the survival of mouse macrophage/preOC RAW264.7 cells in osteoclastogenic culture, suggesting that Ninj1 is important for the survival of preOCs. Finally, analysis of publicly available microarray data sets revealed a potent correlation between high NINJ1 expression and destructive bone disorders in humans. Our data indicate that Ninj1 plays an important role in bone homeostasis by enhancing the survival of preOCs.
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