| First Author | Tan H | Year | 2024 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1870 |
| Issue | 1 | Pages | 166902 |
| PubMed ID | 37816396 | Mgi Jnum | J:358251 |
| Mgi Id | MGI:7561073 | Doi | 10.1016/j.bbadis.2023.166902 |
| Citation | Tan H, et al. (2024) Myo6 mediates osteoclast function and is essential for joint damage in collagen-induced arthritis. Biochim Biophys Acta Mol Basis Dis 1870(1):166902 |
| abstractText | OBJECTIVES: To explore the novel function of MYO6 on Osteoclast differentiation and its joint destruction capacity in Rheumatoid arthritis mice model. METHODS: We examined joint erosion in a collagen-induced arthritis (CIA) mouse model using micro-CT, with the mice having a MYO6 knockout background. Inflammatory cytokines were analyzed using an enzyme-linked immunosorbent assay (ELISA). In vitro, we investigated the osteoclastogenesis ability of bone marrow-derived macrophages isolated from MYO6(-/-) mice and their littermate controls, examining both morphological and functional differences. Furthermore, we explored podosome formation and endosome maturation using immunofluorescence staining. RESULTS: We found that MYO6 deficiency attenuated arthritis development and bone destruction in CIA mice as well as impaired osteoclast differentiation by inhibiting NFATc1 induction. Our findings indicate that MYO6 is essential for the organization of podosomes by modulating the FAK/AKT and integrin-beta3/Src pathways. MYO6 also mediates endosome transportation by regulating the expression of Rab5 and GM130. This may impact the maintenance and functionality of the ruffled border, as well as the regulation of autophagy in osteoclasts. CONCLUSION: Our results demonstrated a critical function of MYO6 in osteoclast differentiation and its potential relevance in experimental arthritis. |
