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

作     者：Hyunsoo Kim Noriko Takegahara Matthew CWalsh Sarah AMiddleton Jiyeon Yu Jumpei Shirakawa Jun Ueda Yoshitaka Fujihara Masahito Ikawa Masaru Ishii Junhyong Kim Yongwon Choi Hyunsoo Kim;Noriko Takegahara;Matthew C. Walsh;Sarah A. Middleton;Jiyeon Yu;Jumpei Shirakawa;Jun Ueda;Yoshitaka Fujihara;Masahito Ikawa;Masaru Ishii;Junhyong Kim;Yongwon Choi

作者机构：Department of Pathology and Laboratory MedicineUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPA 19104USA Department of BiologyDepartment of Computer and Information ScienceSchool of Arts and SciencesProgram in Single Cell BiologyUniversity of PennsylvaniaPhiladelphiaPA 19104USA Research Institute for Microbial DiseasesOsaka UniversitySuitaOsaka 565-0871Japan Department of Immunology and Cell BiologyGraduate School of Medicine and Frontier BiosciencesOsaka UniversitySuitaOsaka 565-0871Japan 

出 版 物：《Bone Research》 (骨研究（英文版）)

年 卷 期：2020年第8卷第1期

页      面：97-106页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学] 

基　　金：supported in part by an NIH grant (AR069546 to Y.C.) The Penn Center for Musculoskeletal Disorders Histology Core (NIH P30-AR069619) a Ministry of Education, Culture, Sports, Science and Technology (MEXT)/Japan Society for the Promotion of Science (JSPS) KAKENHI grant (JP15H05573 to Y.F.) supported in part by Health Research Formula Funds to J.K. from the Commonwealth of Pennsylvania 

主　　题：SF11 osteoclast impaired 

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 ***, 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 *** 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.