Mannan-Binding Lectin Attenuates Inflammatory Arthritis Through the Suppression of Osteoclastogenesis

Frontiers in Immunology

Yunpeng Han¹  Jingwen Xie²  Jia Zhou²  Aiping Yin²  Lijun Dong²  Liyun Zhang²  Yunzhi Liu²  Dantong Li²  Kai Chen²  Yue Zhao³  Jun Wu⁴  Zhengliang Chen⁵  Daming Zuo⁶  Youyi Wang⁷ 

[1] Department of Clinical Laboratory, Guangdong 999 Brain Hospital, Guangzhou, China;Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China;Department of Rheumatology, The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China;Geriatrics Center, General Hospital of Southern Theater Command, PLA, Guangzhou, China;Guangdong Provincial Key Laboratory of Proteomics, Southern Medical University, Guangzhou, China;Microbiome Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China;School of Laboratory Medicine and Biotechnology, Institute of Molecular Immunology, Southern Medical University, Guangzhou, China;

关键词: mannan-binding lectin;    arthritis;    osteoclastogenesis;    receptor activator of nuclear factor-κB ligand;    p38;   

DOI  :  10.3389/fimmu.2019.01239

来源: DOAJ

【 摘 要 】

Mannan-binding lectin (MBL) is a vital element in the host innate immune system, which is primarily produced by the liver and secreted into the circulation. Low serum level of MBL is reported to be associated with an increased risk of arthritis. However, the underlying mechanism by which MBL contributes to the pathogenesis of arthritis is poorly understood. In this study, we investigated the precise role of MBL on the course of experimental murine adjuvant-induced arthritis (AIA). MBL-deficient (MBL−/−) AIA mice showed significantly increased inflammatory responses compared with wild-type C57BL/6 AIA mice, including exacerbated cartilage damage, enhanced histopathological features and high level of tartrate-resistant acid phosphatase (TRAP)-positive cells. MBL protein markedly inhibited the osteoclast formation from human blood monocytes induced by receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in vitro. Mechanistic studies established that MBL inhibited osteoclast differentiation via down-regulation of p38 signaling pathway and subsequent nuclear translocation of c-fos as well as activation of nuclear factor of activated T-cells c1 (NFATc1) pathway. Importantly, we have provided the evidence that concentrations of MBL correlated negatively with the serum levels of amino-terminal propeptide of type I procollagen (PINP) and C-terminal telopeptide of type I collagen (β-CTX), serum markers of bone turnover, in patients with arthritis. Our study revealed an unexpected function of MBL in osteoclastogenesis, thus providing new insight into inflammatory arthritis and other bone-related diseases in patients with MBL deficiency.

【 授权许可】

Unknown