1. Academic Validation
  2. Fusion and hemagglutinin proteins of canine distemper virus promote osteoclast formation through NF-κB dependent and independent mechanisms

Fusion and hemagglutinin proteins of canine distemper virus promote osteoclast formation through NF-κB dependent and independent mechanisms

  • Exp Cell Res. 2019 May 15;378(2):171-181. doi: 10.1016/j.yexcr.2019.03.020.
Wei Wang 1 Wei Feng 2 Dongfang Li 1 Shanshan Liu 1 Yuan Gao 1 Zhongxin Zhao 3 Qianyun Fu 3 Lina Yan 3 Wenwen Zheng 3 Minqi Li 4 Xuexing Zheng 5
Affiliations

Affiliations

  • 1 Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, China.
  • 2 Department of Endodontics, Jinan Stomatological Hospital, Jinan, China.
  • 3 School of Public Health, Shandong University, Jinan, China.
  • 4 Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, China. Electronic address: liminqi@sdu.edu.cn.
  • 5 School of Public Health, Shandong University, Jinan, China. Electronic address: zhengxx2513@hotmail.com.
Abstract

Paget's disease (PD) features abnormal osteoclasts (OC) which sharply increase in number and size and then intensely induce bone resorption. The purpose of this study was to determine the direct effects of canine distemper virus (CDV) and its fusion protein and hemagglutinin protein (F + H) on receptor activator of nuclear factor kappa-B ligand (RANKL) induced OC formation in vitro. Immunofluorescence assay, OC morphological and functional detection, intracellular signaling pathway detection, Real-Time PCR analysis and ELISA were applied in this study. Immunofluorescence assay provided the conclusive proof that CDV can infect and replicate in RAW264.7 mouse monocyte cell line, primary human peripheral blood mononuclear cells (PBMC) and their further fused OC. Both CDV and F + H significantly promoted OC formation and bone resorption ability induced by RANKL. Meanwhile, intracellular signaling transduction analysis revealed CDV and F + H specifically upregulated the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) induced by RANKL, respectively. Furthermore, without RANKL stimulation, both CDV and F + H slightly induced OC-like cells formation in RAW264.7 cell line even in the presence of NF-κB Inhibitor. F + H upregulate OC differentiation and activity through modulation of NF-κB signaling pathway, and induce OC precursor cells merging dependent on the function of glycoproteins themselves. These results meant that F and H proteins play a pivotal role in CDV supporting OC formation. Moreover, this work further provide a new research direction that F and H proteins in CDV should be considered as a trigger during the pathogenesis of PD.

Keywords

Canine distemper virus; Fusion and hemagglutinin protein; NF-κB signaling pathway; Osteoclast; Paget's disease.

Figures
Products