| Autor: |
Minhee Kim, Jin Hee Park, Miyeon Go, Nawon Lee, Jeongin Seo, Hana Lee, Doyong Kim, Hyunil Ha, Taesoo Kim, Myeong Seon Jeong, Suree Kim, Han Sung Kim, Dongmin Kang, Hyunbo Shim, Soo Young Lee |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Bone Research, Vol 12, Iss 1, Pp 1-14 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2095-6231 |
| DOI: |
10.1038/s41413-024-00326-8 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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