ANGPTL2 deletion inhibits osteoclast generation by modulating NF-κB/MAPKs/Cyclin pathways

Biochemical and Biophysical Research Communications
Wei-Ming LiDe-Chen Ding

Abstract

Osteoclasts are multinucleated cells essential for bone-resorption. Successful repair of bone defciencies still remains a great challenge worldwide. The signaling factor angiopoietin-like protein 2 (ANGPTL2), one of eight ANGPTL proteins, functions in maintenance of tissue homeostasis partly through regulating inflammation. In the study, ANGPTL2 expression was promoted during osteoclast development and that suppressing ANGPTL2 alleviated osteoclast production regulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). The results suggested that ANGPTL2 knockdown inhibited M-CSF-caused proliferation of osteoclast precursor cells. Further, ANGPTL2 silence reduced nuclear factor of activated T cell c 1 (NFATC1) and NFATC4 expressions in M-CSF-treated cells, along with decreased Runx2, OPN and Colla1. Moreover, silencing ANGPTL2 down-regulated M-CSF-promoted expressions of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and chemoattractant protein-1 (CCL-2). Consistently, ANGPTL2 knockdown reduced M-CSF-enhanced activation of IKKα, IκBα and nuclear factor κB (NF-κB) and mitogen-activated protein kinases (MAPKs) (p38 MAPK, ERK1/2 MAPK and...Continue Reading

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