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RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts
- Title
- RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts
- Authors
- Kim; Minhee; Park; Jin Hee; Go; Miyeon; Lee; Nawon; Seo; Jeongin; Hana; Doyong; Ha; Hyunil; Taesoo; Jeong; Myeong Seon; Suree; Han Sung; Kang; Dongmin; Shim; Hyunbo; Soo Young
- Ewha Authors
- 이수영; 김태수; 박진희; 김수리
- SCOPUS Author ID
- 이수영; 김태수; 박진희
- Issue Date
- 2024
- Journal Title
- Bone Research
- ISSN
- 2095-4700
- Citation
- Bone Research vol. 12, no. 1
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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. © The Author(s) 2024.
- DOI
- 10.1038/s41413-024-00326-8
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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