| First Author | Kim M | Year | 2024 |
| Journal | Bone Res | Volume | 12 |
| Issue | 1 | Pages | 29 |
| PubMed ID | 38744829 | Mgi Jnum | J:354513 |
| Mgi Id | MGI:7734617 | Doi | 10.1038/s41413-024-00326-8 |
| Citation | Kim M, et al. (2024) RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts. Bone Res 12(1):29 |
| abstractText | 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. |
