박진희 (이화여자대학교) | 한빛사논문 > 한빛사

한빛사논문

조회300

이화여자대학교

Bone Res., May 15 2024, 12 (1) | https://doi.org/10.1038/s41413-024-00326-8 RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts

Minhee Kim¹, Jin Hee Park^1,2, Miyeon Go¹, Nawon Lee¹, Jeongin Seo¹, Hana Lee³, Doyong Kim³, Hyunil Ha⁴, Taesoo Kim⁴, Myeong Seon Jeong⁵, Suree Kim⁶, Taesoo Kim^1,2,7, Han Sung Kim³, Dongmin Kang^1,6, Hyunbo Shim¹ and Soo Young Lee^1,2,7

¹Department of Life Science, Ewha Womans University, Seoul 03760, South Korea;

²The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 03760, South Korea;

³Department of Biomedical Engineering, Yonsei University, Wonju 26493, South Korea;

⁴KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea;

⁵Chuncheon Center, Korea Basic Science Institute, Chuncheon 24341, South Korea;

⁶Fluorescence Core Imaging Center and Bioimaging Data Curation Center, Ewha Womans University, Seoul 03760, South Korea and

⁷Multitasking Macrophage Research Center, Ewha Womans University, Seoul 03760, South Korea

Correspondence: Soo Young Lee

These authors contributed equally: Minhee Kim, Jin Hee Park

Abstract

Mature osteoclasts degrade bone matrix by exocytosis of active proteases from secretory lysosomes through a ruffled border. However, the molecular mechanisms underlying lysosomal trafficking and secretion in osteoclasts remain largely unknown. Here, we show with GeneChip analysis that RUN and FYVE domain-containing protein 4 (RUFY4) is strongly upregulated during osteoclastogenesis. Mice lacking Rufy4 exhibited a high trabecular bone mass phenotype with abnormalities in osteoclast function in vivo. Furthermore, deleting Rufy4 did not affect osteoclast differentiation, but inhibited bone-resorbing activity due to disruption in the acidic maturation of secondary lysosomes, their trafficking to the membrane, and their secretion of cathepsin K into the extracellular space. Mechanistically, RUFY4 promotes late endosome-lysosome fusion by acting as an adaptor protein between Rab7 on late endosomes and LAMP2 on primary lysosomes. Consequently, Rufy4-deficient mice were highly protected from lipopolysaccharide- and ovariectomy-induced bone loss. Thus, RUFY4 plays as a new regulator in osteoclast activity by mediating endo-lysosomal trafficking and have a potential to be specific target for therapies against bone-loss diseases such as osteoporosis.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-16)
연구진국내 연구진
분야 생명과학 > 면역학

댓글 작성 로그인

CV 열람하기

연락처 보기