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IL-35 prevent bone loss through promotion of bone formation and angiogenesis in rheumatoid arthritis
S. Liu1, Y. Li2, L. Xia3, H. Shen4, J. Lu5
- Department of Rheumatology and Immunology, the First Affiliated Hospital of China Medical University, Shenyang, China.
- Department of Rheumatology and Immunology, the First Affiliated Hospital of China Medical University, Shenyang, China.
- Department of Rheumatology and Immunology, the First Affiliated Hospital of China Medical University, Shenyang, China.
- Department of Rheumatology and Immunology, the First Affiliated Hospital of China Medical University, Shenyang, China.
- Department of Rheumatology and Immunology, the First Affiliated Hospital of China Medical University, Shenyang, China. lujingtan@163.com
CER11664
2019 Vol.37, N°5
PI 0820, PF 0825
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PMID: 30767867 [PubMed]
Received: 27/08/2018
Accepted : 07/12/2018
In Press: 11/02/2019
Published: 29/08/2019
Abstract
OBJECTIVES:
Angiogenesis in bone and osteogenesis appear to be closely linked, suggesting the existence of molecular crosstalk between pro-angiogenic molecules and osteoblasts. The pro-angiogenic molecules vascular endothelial growth factor (VEGF) with its receptors Flt-1, Flk-1 and fibroblast growth factor (FGF)-2 play a crucial role in born formation, an early and critical event in the pathogenesis of rheumatoid arthritis (RA). Interleukin (IL)-35 is demonstrated to be an anti-inflammatory cytokine in RA. However, the mechanisms involved are not fully understood. This study aims to investigate whether IL-35 has an impact on angiogenesis in osteoblasts and its related signalling pathway in RA.
METHODS:
The effects of IL-35 on osteoblasts proliferation, apoptosis and pro-angiogenic molecules mRNA and protein were examined using osteoblast-like MC3T3E1 cells in vitro. The effects of IL-35 on proliferation and apoptosis were examined using cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Pro-angiogenic molecules expression were assessed by real time PCR and ELISA, respectively. The signalling pathway between IL-35, bone formation, angiogenesis and signalling pathway was also investigated.
RESULTS:
IL-35 promoted osteoblasts proliferation and inhibited apoptosis in a dose-dependent manner in vitro. IL-35 increased basal and TNF-α induced pro-angiogenic molecules expression by osteoblasts. Blocking the Th17/IL-17 signalling pathway with plumbagin inhibited the pro-angiogenic effects of IL-35 in osteoblasts.
CONCLUSIONS:
These results suggested that IL-35 promotes bone formation and angiogenesis by fostering osteoblasts proliferation, inhibiting apoptosis and upregulating pro-angiogenic molecules through Th17/IL-17 related-signalling pathway. Our findings extend the current understanding of mechanisms modulating bone formation and angiogenesis in RA.
