PTPRJ promotes osteoclast maturation and activity by inhibiting Cbl?mediated ubiquitination of NFATc1 in late osteoclastogenesis

Bone-resorbing osteoclasts (OCLs) are multinucleated phagocytes, whose central roles in regulating bone formation and homeostasis critical for normal health development. OCLs produced from precursor monocytes a multistage process that includes initial differentiation, cell–cell fusion, subsequent functional morphological maturation; the molecular regulation of osteoclastogenesis is not fully understood. Here, we identify receptor-type protein tyrosine phosphatase PTPRJ as an essential regulator specifically OCL maturation. Monocytes PTPRJ-deficient (JKO) mice differentiate fuse normally, but their maturation into ability to degrade severely inhibited. In agreement, lacking throughout bodies or only exhibit increased mass due reduced OCL-mediated resorption. We further show promotes by dephosphorylating M-CSF receptor (M-CSFR) Cbl, thus reducing ubiquitination degradation key osteoclastogenic transcription factor NFATc1. Loss increases NFATc1 reduces its amounts at later stages osteoclastogenesis, thereby inhibiting fulfills cell-autonomous role promoting balancing between pro- anti-osteoclastogenic activities M-CSFR maintaining expression during late osteoclastogenesis.