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Interleukin 29 inhibits RANKL‐induced osteoclastogenesis via activation of JNK and STAT, and inhibition of NF‐&kgr;B and NFATc1

Q. Peng,A. Luo,Zihao Zhou,W. Xuan,M. Qiu,Qin Wu,Lingxiao Xu,X. Kong,Miaojia Zhang,W. Tan,M. Xue,F. Wang

Published 2019 in Cytokine

ABSTRACT

&NA; Interleukin (IL)‐29 is known to modulate immune functions of monocytes or macrophages. In this study, we investigated the effect and its underlying mechanism of IL‐29 on receptor activator of nuclear factor &kgr;B ligand (RANKL)‐induced osteoclastogenesis using murine macrophage cell line RAW264.7 cells and bone‐marrow‐derived monocyte/macrophage precursor cells (BMMs), and human peripheral blood mononuclear cells (PBMCs). In response to human recombinant IL‐29, cell viability and apoptosis were assessed by Cell Counting Kit‐8 and flow cytometry; the osteoclast formation and activity by tartrate‐resistant acid phosphatase (TRAP) staining and pit formation assay, respectively; the expression and activation of molecules that associated with osteoclastogenesis by real time‐PCR, immunoblotting or immunofluorescent analysis. IL‐28 receptor &agr; (IL‐28R&agr;), a specific receptor of IL‐29 was expressed on RAW264.7 cells. Although IL‐29 did not affect the viability and apoptosis of RAW264.7 cells, it inhibited multinucleated cells in the differentiation of osteoclastogenesis, the bone‐resorbing activity of mature osteoclasts and osteoclastic specific genes expression including TRAP, cathepsin K (CTSK), nuclear factor of activated T‐cells, cytoplasmic 1 (NFATc1), C‐Fos and matrix metallopeptidase 9 (MMP‐9). This inhibitory effect of IL‐29 was confirmed on BMMs and PBMCs and mediated via IL‐28R&agr; through the activation of Stat1 and 3 and the suppression of nuclear factor kappa B (NF‐&kgr;B) and NFATc1 nuclear translocation in RAW264.7 cells. In conclusion, IL‐29 inhibited osteoclastogenesis via activation of STAT signaling pathway, prevention of NF‐&kgr;B activation and NFATc1 translocation, and suppression of downstream osteoclastogenic genes expression.

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