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.

Adipokine Signaling Pathways in Osteoarthritis

“…Although leptin at 100 ng/ml failed to activate STAT 3, it could induce STAT 1α phosphorylation in the chondrocytes of obese patients ( Pallu et al, 2010 ). Leptin receptor activation initiated by leptin binding was reported to activate multiple signaling pathways including JAK/STAT ( Eldjoudi et al, 2022 ).…”

“…It’s close association with OA have been widely reported in literature ( Collins et al, 2020 ). Clinical data has shown that there was a positive correlation between synovial adipokine level and OA activity index in elderly women with knee OA ( Eldjoudi et al, 2022 ; Ilia et al, 2022 ).…”

Organokines in Rheumatoid Arthritis: A Critical Review

“…It is an organokine that affects the activity of bone morphogenetic proteins (BMPs) and is an inhibitor of the Wnt/β-catenin metabolic pathway in bone cells. Although sclerostin is as an osteocyte-specific protein, recent studies have shown that several additional cell types express SOST and can produce the sclerostin protein, such as osteoclasts, chondrocytes, and in tissues such as the kidney, heart, and liver [ 73 , 84 , 85 , 86 ].…”

“…Inhibiting the Wnt pathway by SOST involves activating caspases and pro-inflammatory cytokines produced by the synovial membrane, increasing bone resorption, and stimulating soluble antagonists of the canonical Wnt/βcatenin signaling pathway with subsequent inhibition of proliferation, maturation, and differentiation of osteoblast progenitors. Sclerostin can also antagonize BMP signaling directly by inhibiting BMP-7 secretion, leading to intracellular retention and proteasomal degradation of BMP-7, and blocking BMP signaling selectively in osteocytes that simultaneously synthesize sclerostin and BMP-7 proteins [ 73 , 75 , 84 , 85 , 86 ].…”

“…Bone loss, erosion, and systemic osteoporosis with an increased risk of fractures are seen mainly in RA. Therefore, sclerostin inhibition is a powerful tool for improving bone repair in inflammatory arthritis [ 73 , 75 , 84 , 85 , 86 ].…”