TY - JOUR
T1 - Phospholipase Cγ2 mediates RANKL-stimulated lymph node organogenesis and osteoclastogenesis
AU - Chen, Yabing
AU - Wang, Xiaohong
AU - Di, Lie
AU - Fu, Guoping
AU - Chen, Yuhong
AU - Bai, Li
AU - Liu, Jianzhong
AU - Feng, Xu
AU - McDonald, Jay M.
AU - Michalek, Sue
AU - He, Yinghong
AU - Yu, Mei
AU - Fu, Yang Xin
AU - Wen, Renren
AU - Wu, Hui
AU - Wang, Demin
PY - 2008/10/24
Y1 - 2008/10/24
N2 - Phospholipase Cγ2 (PLCγ2) is an important signaling effector of multiple receptors in the immune system. Here we show that PLCγ2- deficient mice displayed impaired lymph node organogenesis but normal splenic structure and Peyer's patches. Receptor activator of NF-κB ligand (RANKL) is a tumor necrosis factor family cytokine and is essential for lymph node organogenesis. Importantly, PLCγ2 deficiency severely impaired RANKL signaling, resulting in marked reduction of RANKL-induced activation of MAPKs, p38 and JNK, but not ERK. The lack of PLCγ2 markedly diminished RANKL-induced activation of NF-κB, AP-1, and NFATc1. Moreover, PLCγ2 deficiency impaired RANKL-mediated biological function, leading to failure of the PLCγ2-deficient bone marrow macrophage precursors to differentiate into osteoclasts after RANKL stimulation. Re-introduction of PLCγ2 but not PLCγ1 restores RANKL-mediated osteoclast differentiation of PLCγ2-deficient bone marrow-derived monocyte/macrophage. Taken together, PLCγ2 is essential for RANK signaling, and its deficiency leads to defective lymph node organogenesis and osteoclast differentiation.
AB - Phospholipase Cγ2 (PLCγ2) is an important signaling effector of multiple receptors in the immune system. Here we show that PLCγ2- deficient mice displayed impaired lymph node organogenesis but normal splenic structure and Peyer's patches. Receptor activator of NF-κB ligand (RANKL) is a tumor necrosis factor family cytokine and is essential for lymph node organogenesis. Importantly, PLCγ2 deficiency severely impaired RANKL signaling, resulting in marked reduction of RANKL-induced activation of MAPKs, p38 and JNK, but not ERK. The lack of PLCγ2 markedly diminished RANKL-induced activation of NF-κB, AP-1, and NFATc1. Moreover, PLCγ2 deficiency impaired RANKL-mediated biological function, leading to failure of the PLCγ2-deficient bone marrow macrophage precursors to differentiate into osteoclasts after RANKL stimulation. Re-introduction of PLCγ2 but not PLCγ1 restores RANKL-mediated osteoclast differentiation of PLCγ2-deficient bone marrow-derived monocyte/macrophage. Taken together, PLCγ2 is essential for RANK signaling, and its deficiency leads to defective lymph node organogenesis and osteoclast differentiation.
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U2 - 10.1074/jbc.M802493200
DO - 10.1074/jbc.M802493200
M3 - Article
C2 - 18728019
AN - SCOPUS:57649174473
SN - 0021-9258
VL - 283
SP - 29593
EP - 29601
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 43
ER -