Lee J H, Ort T, Ma K, Picha K, Carton J, Marsters P A, Lohmander L S, Baribaud F, Song X-Y R, Blake S
Discovery Research, Centocor Research & Development, Radnor, PA 19087, USA.
Osteoarthritis Cartilage. 2009 May;17(5):613-20. doi: 10.1016/j.joca.2008.08.007. Epub 2008 Nov 1.
Resistin is a secreted factor that is elevated in rheumatoid arthritis (RA) and believed to drive joint inflammation in vivo. This study was undertaken to determine if resistin is present in the joint following joint injury and to elucidate the role of resistin in cartilage degradation.
The level of resistin was measured in paired synovial fluid (SF) and serum samples from patients following joint injury (anterior cruciate ligament, ACL or meniscus tear). Localization of resistin was visualized by immunohistochemistry of synovial tissue and cartilage from healthy and OA donors. Mouse and human cartilage cultures were used to assess the effect of resistin on cartilage metabolism.
In trauma patients, resistin levels declined with increasing time post injury. The resistin levels were highest in samples collected up to 1 week following traumatic injury (SF: 2980 pg/ml, serum: 7901 pg/ml) and lowest in samples collected 6-26 years post injury (SF: 686 pg/ml, serum: 5682 pg/ml). Resistin was shown to be expressed in macrophage-like cells in both healthy and OA synovial tissue. Treatment of mouse cartilage cultures with recombinant resistin led to a dose dependent loss of proteoglycan and induction of inflammatory cytokine and PGE(2) production. Recombinant resistin inhibited proteoglycan synthesis in human cartilage explants.
Resistin is elevated both systemically and locally in the weeks immediately following joint injury and has a direct effect on cartilage matrix turnover and cytokine production. Resistin may play a role in the early stages of trauma-induced OA and may represent a new therapeutic target to slow joint destruction in OA.
抵抗素是一种分泌因子，在类风湿关节炎（RA）中水平升高，被认为可在体内驱动关节炎症。本研究旨在确定关节损伤后关节中是否存在抵抗素，并阐明抵抗素在软骨降解中的作用。
测量关节损伤（前交叉韧带、ACL或半月板撕裂）患者配对的滑液（SF）和血清样本中抵抗素的水平。通过对健康和骨关节炎（OA）供体的滑膜组织和软骨进行免疫组织化学来观察抵抗素的定位。使用小鼠和人类软骨培养物评估抵抗素对软骨代谢的影响。
在创伤患者中，抵抗素水平随损伤后时间的增加而下降。在创伤后1周内采集的样本中抵抗素水平最高（SF：2980 pg/ml，血清：7901 pg/ml），在损伤后6 - 26年采集的样本中最低（SF：686 pg/ml，血清：5682 pg/ml）。抵抗素在健康和OA滑膜组织中的巨噬细胞样细胞中均有表达。用重组抵抗素处理小鼠软骨培养物导致蛋白聚糖剂量依赖性丢失，并诱导炎性细胞因子和PGE(2)产生。重组抵抗素抑制人软骨外植体中的蛋白聚糖合成。
在关节损伤后的数周内，抵抗素在全身和局部均升高，对软骨基质周转和细胞因子产生有直接影响。抵抗素可能在创伤诱导的OA早期阶段起作用，可能代表一种减缓OA关节破坏的新治疗靶点。
