Role of IL-32 Gamma on Bone Metabolism in Autoimmune Arthritis

Abstract

IL-32 acts as a pro-inflammatory cytokine by inducing the synthesis of inflammatory molecules as well as promoting the morphological changes involved in the transformation of monocytes into osteoclasts (OCs). Evaluation of the functions of IL-32 has mainly focused on its inflammatory properties, such as involvement in the pathogenesis of various autoimmune diseases. Recently, IL-32 was shown to be involved in bone metabolism, in which it promotes the differentiation and activation of OCs and plays a key role in bone resorption in inflammatory conditions. IL-32γ also regulates bone formation in conditions such as ankylosing spondylitis and osteoporosis. In this review, we summarize the results of recent studies on the role of IL-32γ in bone metabolism in inflammatory arthritis.

Keywords: Ankylosing spondylitis; IL-32; Inflammation; Osteoblasts; Osteoclasts; Rheumatoid arthritis.

Figure 1. Multifaceted roles of IL-32γ in bone metabolism in RA and AS. RA is characterized by bone destruction, whereas AS is characterized by bone formation. In RA, IL-32γ and TNF-α promote OC formation by increasing RANKL production from RA-FLSs and OBs, thereby contributing to inflammatory bone loss in RA. However, in AS, highly elevated IL-32γ in the joint plays a key role in excessive bone formation by enhancing OB differentiation via inhibition of DKK-1.