Phospholipase Cγ2 mediates RANKL-stimulated lymph node organogenesis and osteoclastogenesis

Yabing Chen, Xiaohong Wang, Lie Di, Guoping Fu, Yuhong Chen, Li Bai, Jianzhong Liu, Xu Feng, Jay M. McDonald, Sue Michalek, Yinghong He, Mei Yu, Yang Xin Fu, Renren Wen, Hui Wu, Demin Wang

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)29593-29601
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number43
DOIs
StatePublished - Oct 24 2008

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Chen, Y., Wang, X., Di, L., Fu, G., Chen, Y., Bai, L., Liu, J., Feng, X., McDonald, J. M., Michalek, S., He, Y., Yu, M., Fu, Y. X., Wen, R., Wu, H., & Wang, D. (2008). Phospholipase Cγ2 mediates RANKL-stimulated lymph node organogenesis and osteoclastogenesis. Journal of Biological Chemistry, 283(43), 29593-29601. https://doi.org/10.1074/jbc.M802493200