Leptin in Osteoarthritis and Rheumatoid Arthritis: Player or Bystander?

Abstract

White adipose tissue (WAT) is a specialized tissue whose main function is lipid synthesis and triglyceride storage. It is now considered as an active organ secreting a plethora of hormones and cytokines namely adipokines. Discovered in 1994, leptin has emerged as a key molecule with pleiotropic functions. It is primarily recognized for its role in regulating energy homeostasis and food intake. Currently, further evidence suggests its potent role in reproduction, glucose metabolism, hematopoiesis, and interaction with the immune system. It is implicated in both innate and adaptive immunity, and it is reported to contribute, with other adipokines, in the cross-talking networks involved in the pathogenesis of chronic inflammation and immune-related diseases of the musculo-skeletal system such as osteoarthritis (OA) and rheumatoid arthritis (RA). In this review, we summarize the most recent findings concerning the involvement of leptin in immunity and inflammatory responses in OA and RA.

Keywords: inflammation; leptin; leptin receptor; osteoarthritis; rheumatoid arthritis.

Figure 1

Leptin impact in OA pathophysiology. Leptin modulates the inflammatory environment in the joint, the imbalance between catabolic and anabolic factors, and remodeling of bone and cartilage. It also activates chondrocytes and production of pro-inflammatory mediators including IL-6, IL-8, NO, PG, NOS2, and COX2 and up-regulates metalloproteinases (MMP) production leading to extracellular matrix (ECM) degradation. It modulates cytokine production in synovial fibroblasts and bone remodeling imbalance exacerbating cartilage destruction and OA progression.

Figure 2

Leptin effect on RA key effector cells. Leptin enhances Th17 proliferation, B cell activation, and macrophage production of TNF and Il-6. It activates FLS migration and secretion of IL-8. It acts on chondrocytes by activating NOS expression and adhesion molecules leading to lymphocyte infiltration to the inflamed joints and degradation of articular cartilage.