MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, Queen Elizabeth Hospital, University of Birmingham, Birmingham B15 2WB, UK.
Division of Pharmacy and Optometry, School of Health Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester M13 9PL, UK.
Int J Mol Sci. 2021 Jun 23;22(13):6719. doi: 10.3390/ijms22136719.
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.
肥胖会增加髋骨骨关节炎（OA）的风险。最近的研究表明，脂肪因子细胞外烟酰胺磷酸核糖转移酶（eNAMPT 或内脂素）可诱导软骨细胞中白细胞介素 6 和基质金属蛋白酶（MMPs）的产生，提示其可能促进关节软骨降解。然而，细胞外 visfatin 对人关节软骨组织的功能影响，以及其在不同 BMI 的髋 OA 患者关节中的表达，尚未有报道。我们从接受关节置换手术的患者中收集髋 OA 关节组织。用重组人内脂素来刺激软骨外植体。通过 ELISA 和 Luminex 测量促炎细胞因子和 MMPs。通过免疫组织化学确定软骨组织中 visfatin 表达的定位。通过定量测定蛋白聚糖释放来确定软骨基质降解。肥胖的髋 OA 患者的滑膜组织中 visfatin 的表达升高，并且与软骨损伤区域的 MMP-13 共定位。Visfatin 促进髋 OA 软骨蛋白聚糖的降解，并诱导促炎细胞因子（IL-6、MCP-1、CCL20 和 CCL4）和 MMPs 的产生。肥胖的髋 OA 关节中 visfatin 的高表达及其对髋软骨组织的功能影响表明，它在肥胖的髋 OA 患者中软骨完整性丧失中发挥核心作用。
