Small interference RNA against leptin deactivated directly MMP-13, which was upregulated after leptin's epigenetic reactivation, raising the issue of leptin's therapeutic potential for osteoarthritis.
We investigated the signaling pathway involved in IL-8 production caused by leptin in both rheumatoid arthritis synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OASF).
The expression of leptin, adiponectin and their receptors, as well as cartilage-specific genes was examined in chondrocytes obtained from patients with osteoarthritis either directly after cells harvest or after culture in monolayer or in alginate beads.
Leptin and vascular cell adhesion molecules-1 (VCAM-1) are two important mediators in obesity-related osteoarthritis, while the molecular mechanism linking leptin to VCAM-1 production is still obscure.
The findings supporting leptin as a causative link between obesity and OA offer leptin as a potential target to the development of disease-modifying drugs for osteoarthritis (DMOAD), especially for obese patients.
Since leptin levels were increased in synovial fluid compared to serum in OA patients, it was suggested that joint cells themselves could produce leptin.
In conclusion, UCP4, whose expression was suppressed by leptin, may be involved in the ROS production and apoptosis of chondrocytes, thus contributing to the OA pathogenesis.
The metabolic origin of OA has been partially attributed to the involvement of adipokines, such as leptin, the levels of which are significantly and positively correlated with cartilage degeneration in OA patients.
These data indicate that RSV promotes Sirt1 levels, inhibits the endogenous expression of leptin by OA osteoblasts and can promote the Wnt/β-catenin and Erk1/2 signaling pathways, which are altered in these cells.
The conditioned media of IFP and subcutaneous adipose tissue from OA patients were used to determine the production of leptin and adiponectin, and to stimulate chondrocytes and fibroblast-like synoviocytes (FLS).
Serum leptin levels were correlated with low vitamin D, reduced muscle strength and functional impairment, suggesting that serum leptin might serve as a biomarker reflecting physical performance in OA patients.
This Review discusses the latest findings regarding the role of leptin in the immune system and metabolism, with particular emphasis on its effect on autoimmune and/or inflammatory rheumatic diseases, such as rheumatoid arthritis and osteoarthritis.
Adipokines (e.g., visfatin, resistin, leptin) are adipocyte-derived factors with immunomodulatory properties and might influence differentiation of bone marrow-derived mesenchymal stem cells (MSC) in osteoarthritis (OA) and osteoporosis (OP).
Interleukin-6 and leptin levels are associated with preoperative pain severity in patients with osteoarthritis but not with acute pain after total knee arthroplasty.