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

Abstract

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.

Tanshinone IIA Suppresses Proliferation and Inflammatory Cytokine Production of Synovial Fibroblasts from Rheumatoid Arthritis Patients Induced by TNF-α and Attenuates the Inflammatory Response in AIA Mice

“…Eighteen male C57BL/6 mice, about 20 g in body weight each, were divided into three groups randomly: the normal group, AIA model group, and AIA model with Tan IIA treatment group. The protocol for inducing the AIA model was as previously described (Atkinson and Nansen, 2017;Dong et al, 2019;Du et al, 2019;Grötsch et al, 2019), adjusted on some points. The experimental timeline for AIA is shown in Figure 1.…”

“…simultaneously. Body weight and mediolateral knee joint diameter were monitored by experimenters blinded to the experimental design every 5 days (Frey et al, 2018;Dong et al, 2019;Du et al, 2019).…”

Hypolipidemic Effects of β-Glucans, Mannans, and Fucoidans: Mechanism of Action and Their Prospects for Clinical Application

“…In mice, MBL deficiency does not affect antibody production [62]. MBL is a key receptor in the innate immune system and is present in blood plasma; MBL is produced in the liver in response to infection and belongs to the group of acute-phase proteins [63,64]. MLB binds to specific carbohydrate motifs on the membranes of various pathogens, followed by stimulation of the immune system via the lectin pathway [65].…”

“…Therapeutic use of MBL for MBL-deficient patients with a respiratory tract infection is potentially possible [67]. MBL2 gene polymorphism is associated with various inflammatory diseases (without consistent changes in MBL serum levels); therefore, further elucidation of the role of MBL in these diseases is needed [63].…”

Status of mannose-binding lectin (MBL) and complement system in COVID-19 patients and therapeutic applications of antiviral plant MBLs

“…Dong et al indicated that sMBL levels in patients with arthritis are negatively correlated with the serum levels of markers of bone turnover [53]. sMBL therapy may ameliorate various immunodeficiency syndromes.…”