Ig SF11 regulates osteoclast differentiation through association with the scaffold protein PSD-95

更新时间:2023-05-28

【摘要】Osteoclasts are multinucleated, giant cells derived from myeloid progenitors. While receptor activator of NF-κB ligand(RANKL)stimulation is the primary driver of osteoclast differentiation, additional signaling further contributes to osteoclast maturation.Here, we demonstrate that immunoglobulin superfamily member 11(Ig SF11), whose expression increases during osteoclast differentiation, regulates osteoclast differentiation through interaction with postsynaptic density protein 95(PSD-95), a scaffold protein with multiple protein interaction domains. Ig SF11 deficiency in vivo results in impaired osteoclast differentiation and bone resorption but no observed defect in bone formation. Consequently, Ig SF11-deficient mice exhibit increased bone mass.Using in vitro osteoclast culture systems, we show that Ig SF11 functions through homophilic interactions. Additionally, we demonstrate that impaired osteoclast differentiation in Ig SF11-deficient cells is rescued by full-length Ig SF11 and that the Ig SF11-PSD-95 interaction requires the 75 C-terminal amino acids of Ig SF11. Our findings reveal a critical role for Ig SF11 during osteoclast differentiation and suggest a role for Ig SF11 in a receptor-and signal transduction molecule-containing protein complex.

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