targeted disruption of ephrin b1 in cells of myeloid lineage increases osteoclast differentiation and bone resorption in mice靶向破坏骨髓细胞谱系的ephrin b1增加破骨细胞分化和骨吸收在老鼠身上.pdf

Targeted Disruption of Ephrin B1 in Cells of Myeloid Lineage Increases Osteoclast Differentiation and Bone Resorption in Mice 1 1 4 1,2 1,2 Shaohong Cheng , Shien Lucy Zhao , Brittany Nelson , Chandrasekhar Kesavan , Xuezhong Qin , Jon Wergedal1,2,3, Subburaman Mohan1,2,3,4, Weirong Xing1,2* 1 Musculoskeletal Disease Center, Jerry L Pettis VA Medical Center, Loma Linda, California, United States of America, 2 Department of Medicine, Loma Linda University, Loma Linda, California, United States of America, 3 Department of Biochemistry, Loma Linda University, Loma Linda, California, United States of America, 4 Department of Physiology, Loma Linda University, Loma Linda, California, United States of America Abstract Disruption of ephrin B1 in collagen I producing cells in mice results in severe skull defects and reduced bone formation. Because ephrin B1 is also expressed during osteoclast differentiation and because little is known on the role of ephrin B1 reverse signaling in bone resorption, we examined the bone phenotypes in ephrin B1 conditional knockout mice, and studied the function of ephrin B1 reverse signaling on osteoclast differentiation and resorptive activity. Targeted deletion of ephrin B1 gene in myeloid lineage cells resulted in reduced trabecular bone volume, trabecular number and trabecular thickness caused by increased TRAP positive osteoclasts and bone resorption. Histomorphometric analyses found bone formation parameters were not changed in ephrin B1 knockout mice. Treatment of wild-type precursors with clustered soluble EphB2-Fc inhibited RANKL induced formation of multinucleated osteoclasts, and bone resorption pits. The s