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.
Highlights
Osteoarthritis (OA) is a leading cause of pain, disability, and shortening of adultworking life, and there are currently no approved disease-modifying OA drugs (DMOADs).In attempting to identify personalised DMOADs, it is recognised that OA is a heterogeneous disease involving multiple tissues within the joint [1,2]
In reference to de Boer et al [11] (2012), which suggested that adipokines may play important roles in OA development due to the heightened expression in OA patient serum, we first investigated the expression of eNAMPT in patient serum
This study is the first to report the functional effects of extracellular visfatin on human OA cartilage tissue, and to profile its expression and localisation in the joint tissues of patients with hip OA of varying BMI
Summary
In attempting to identify personalised DMOADs, it is recognised that OA is a heterogeneous disease involving multiple tissues within the joint [1,2]. One group of proteins that provide a link between obesity and joint damage are the adipose-secreted cytokines (adipokines), which are known regulators of metabolism [5,6,7,8,9,10] and the inflammatory response [11,12,13,14,15,16,17,18]. Previous research has demonstrated differential serum adipokine levels in relation to pathological indices associated with OA.
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