eNAMPT Is Localised to Areas of Cartilage Damage in Patients with Hip Osteoarthritis and Promotes Cartilage Catabolism and Inflammation

Abstract

Obesity increases the risk of hip osteoarthritis (OA). Recent studies have shown that adipokine extracellular nicotinamide phosphoribosyltransferase (eNAMPT or visfatin) induces the production of IL-6 and matrix metalloproteases (MMPs) in chondrocytes, suggesting it may promote articular cartilage degradation. However, neither the functional effects of extracellular visfatin on human articular cartilage tissue, nor its expression in the joint of hip OA patients of varying BMI, have been reported. Hip OA joint tissues were collected from patients undergoing joint replacement surgery. Cartilage explants were stimulated with recombinant human visfatin. Pro-inflammatory cytokines and MMPs were measured by ELISA and Luminex. Localisation of visfatin expression in cartilage tissue was determined by immunohistochemistry. Cartilage matrix degradation was determined by quantifying proteoglycan release. Expression of visfatin was elevated in the synovial tissue of hip OA patients who were obese, and was co-localised with MMP-13 in areas of cartilage damage. Visfatin promoted the degradation of hip OA cartilage proteoglycan and induced the production of pro-inflammatory cytokines (IL-6, MCP-1, CCL20, and CCL4) and MMPs. The elevated expression of visfatin in the obese hip OA joint, and its functional effects on hip cartilage tissue, suggests it plays a central role in the loss of cartilage integrity in obese patients with hip OA.

Differential Metabotypes in Synovial Fibroblasts and Synovial Fluid in Hip Osteoarthritis Patients Support Inflammatory Responses

“…Importantly, in the OA joint, we have reported that obesity imprints an inflammatory activated synovial fibroblast phenotype, with fibroblasts from obese OA patients being more proliferative and secreting greater amounts of IL-6 [ 13 , 14 ]. Importantly, obesity is a major risk factor for the development of OA in both weight-bearing joints such as the knee [ 22 , 23 ] and hip [ 24 ], as well as non-weight bearing joints such as the hand [ 25 ], promoting cartilage degeneration [ 26 ] and sclerotic subchondral bone pathology [ 27 ]. Therefore, understanding whether metabolic differences underpin this obese inflammatory activated OA synovial fibroblasts could provide a new rationale for targeting synovial joint inflammation in OA.…”

Nesfatin-1 stimulates CCL2-dependent monocyte migration and M1 macrophage polarization: implications for rheumatoid arthritis therapy

“…Interestingly, several adipokines have shown similar effects in joint diseases. For instance, resistin increases CCL2 expression in osteoarthritis (OA) synovial broblasts (31), while visfatin and adiponectin upregulate levels of several chemokines in OA and RA (32,33). Thus, our evidence showing that nesfatin-1 induces increases in CCL2 expression provides a new insight into adipokine involvement in joint disease.…”

Nesfatin-1 Stimulates CCL2-dependent Monocyte Migration And M1 Macrophage Polarization: Implications For Rheumatoid Arthritis Therapy

“…Interestingly, several adipokines have shown similar effects in joint diseases. For instance, resistin increases CCL2 expression in osteoarthritis (OA) synovial fibroblasts 36 , while visfatin and adiponectin upregulate levels of several chemokines in OA and RA 37 , 38 . Thus, our evidence showing that nesfatin-1 induces increases in CCL2 expression provides a new insight into adipokine involvement in joint disease.…”