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Genes Cells ; 25(11): 707-717, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32916757

RESUMO

Osteoclasts are multinucleated cells responsible for bone resorption. Src homology 3 (SH3) domain-containing protein-2 (SH3P2)/osteoclast-stimulating factor-1 regulates osteoclast differentiation, but its exact role remains elusive. Here, we show that SH3P2 suppresses osteoclast differentiation. SH3P2 knockout (KO) mice displayed decreased femoral trabecular bone mass and enhanced localization of osteoclasts on the tibial trabecular bone surface, suggesting that SH3P2 suppresses bone resorption by osteoclasts. Osteoclast differentiation based on cellular multinuclearity induced by macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL) was enhanced in bone marrow-derived macrophages lacking SH3P2. RANKL induced SH3P2 dephosphorylation, which increased the association of actin-dependent motor protein myosin 1E (Myo1E) with SH3P2 and thereby prevented Myo1E localization to the plasma membrane. Consistent with this, Myo1E in the membrane fraction increased in SH3P2-KO cells. Together with the attenuated osteoclast differentiation in Myo1E knocked down cells, SH3P2 may suppress osteoclast differentiation by preventing their cell-to-cell fusion depending on Myo1E membrane localization.


Assuntos
Proteínas Musculares/metabolismo , Miosina Tipo I/metabolismo , Osteoclastos/metabolismo , Animais , Células da Medula Óssea/metabolismo , Reabsorção Óssea/metabolismo , Reabsorção Óssea/prevenção & controle , Proteínas de Transporte/metabolismo , Diferenciação Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Fêmur/metabolismo , Hematopoese/efeitos dos fármacos , Fator Estimulador de Colônias de Macrófagos/metabolismo , Macrófagos/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Musculares/fisiologia , Miosina Tipo I/fisiologia , Miosinas/metabolismo , Osteoclastos/fisiologia , Ligante RANK/metabolismo , Transdução de Sinais/efeitos dos fármacos
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