Adipokines and its role in osteoarthritis

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Adipokines are a family of cytokines or hormones secreted by white adipocytes that mainly include leptin, adiponectin, resistin and visceral adipokines. Back in 2003, it was first reported by  that leptin was detectable in osteoarthritis (OA) articular fluid[1]. Moreover, the level of leptin expression in the OA joint fluid was correlated with the degree of cartilage destruction. Further  studies revealed that leptin strongly stimulated anabolism in chondrocytes and induced chondrocyte insulin-like growth factor-1 (insulin like growth factor 1, IGF 1), transforming growth factor β1 (transforming growth factor beta1, TGF β1) synthesis. It was suggested that leptin is closely related to OA and has a regulatory effect on articular cartilage metabolism[2].

Besides, many studies have found that adiponectin, resistin and visceral adipokines can also be detected in joint fluid, and the level of adipokines in joint fluid of OA patients is higher than that in healthy people . Studies of OA in the knee, hip and shoulder found that joint pain was also positively correlated with adipokine levels in the joint fluid. Articular cartilage, synovial membrane and inferior fat pad can produce adipokine, and the receptor for adipokines is expressed in articular chondrocytes and synovium. The level of adipokines in the joint fluid of OA patients is also related to obesity [3]. In addition, some studies have found that obesity affects the response of articular chondrocytes to leptin[4]. It shows that obesity not only has the effect on systemic adipokine levels, but also regulates the production and response of local adipokines in the joint.

There was also a correlation between blood adipokine content and OA. It was Found that serum leptin and adiponectin levels were positively associated with the onset of OA. It showed a positive correlation of between them and the severity of OA. Further studies showed that the levels of adipokines in OA serum and joint fluid were associated with the loss of cartilage degeneration markers and articular cartilage volume, indicating that adipokines are involved in the degenerative process of cartilage[5].

Adipokines increase the production of proinflammatory mediators in articular chondrocytes and synovial fibroblasts, which play an important role in the pathology of OA. It has shown that adipokines induce the expression of nitric oxide synthase (NO synthase, NOS) and cyclooxygenase-2 (cyclooxygenase 2, COX2) in human chondrocytes and articular synovial fibroblasts, with correspondingly increased expression of their products NO, PGE2, IL-6, and IL-8. These inflammatory mediators and cytokines induce the production of local inflammatory factors and cartilage matrix lyases in the joints, which play an important role in the production of OA inflammation and cartilage destruction[6].

Reference

  1. Dumond H, Presle N, Terlain B, Mainard D, Loeuille D, Netter P, Pottie P. Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum. 2003 Nov;48(11):3118-29. doi: 10.1002/art.11303. PMID: 14613274.

  2. Fu Y, Batushansky A, Kinter M, Huebner JL, Kraus VB, Griffin TM. Effects of Leptin and Body Weight on Inflammation and Knee Osteoarthritis Phenotypes in Female Rats. JBMR Plus. 2023 May 5;7(7):e10754. 

  3. Mai NTT, Hang NT, Hanh DH, Le HY, Hinh NV, Ky ND, Tuan NM, Tong HV, Quan DT, Toan NL. Leptin and interleukin-1β levels associated with osteoarthritis in Vietnamese patients: a cross-sectional analysis. Braz J Med Biol Res. 2023 Sep 8;56:e12746. doi: 10.1590/1414-431X2023e12746. PMID: 37703108; PMCID: PMC10496761.

  4. Pallu S, Francin PJ, Guillaume C, et al. Obesity affects the chondrocyte responsiveness to leptin in patients with osteoarthritis[J]. Arthritis Res Ther, 2010, 12(3): R112. DOI: 10.1186/ar3048.

  5. Shumnalieva R, Kotov G, Ermencheva P, Monov S. Pathogenic Mechanisms and Therapeutic Approaches in Obesity-Related Knee Osteoarthritis. Biomedicines. 2023 Dec 20;12(1):9. doi: 10.3390/biomedicines12010009. PMID: 38275369; PMCID: PMC10812969.

  6. Upadhyay P, Kalra D, Nilakhe AS, Aggrawal V, Gupta S. Polyherbal formulation PL02 alleviates pain, inflammation, and subchondral bone deterioration in an osteoarthritis rodent model. Front Nutr. 2023 Nov 16;10:1217051. doi: 10.3389/fnut.2023.1217051. PMID: 38045809; PMCID: PMC10693428.