Department of Orthopedic Surgery, Tainan Hospital, Department of Health, Executive Yuan, Taiwan.
Exp Biol Med (Maywood). 2011 Mar;236(3):334-40. doi: 10.1258/ebm.2010.010319. Epub 2011 Mar 4.
Pro-opiomelanocortin (POMC) is a precursor of various neuropeptides. POMC-derived neuropeptides are potent inflammation inhibitors and immunosuppressants. Evidence that osteoarthritis (OA) is an inflammatory disease is accumulating. We assessed whether intra-articular gene delivery of POMC ameliorates experimentally induced OA in a rat model. OA was induced in Wistar rats by anterior cruciate ligament-transection (ACLT) in the knee of one hind limb. Adenoviral vector encoding human POMC (AdPOMC) was injected intra-articularly into the knee joints after ACLT. The transgene expression and the inflammatory responses were evaluated using immunoblotting, immunohistochemistry and enzyme-linked immunosorbent assay. The treated joints were assessed histologically for manifestations of the disease. Human POMC was expressed in the chondrocytes and synovial membrane after the intra-articular injection. POMC gene transfer reduced nuclear factor-κB activity and the levels of interleukin-1β in HTB-94 chondrosarcoma cells and Raw 264.7 macrophages; it also reduced microvessel density in the synovium. Histological examination showed that symptoms of OA in AdPOMC-treated rats were less severe than in rats treated with either empty adenoviral vector (AdNull) or normal saline. Intra-articular injection of adenoviral vectors expressing POMC significantly suppressed the progression and severity of OA, and reduced inflammatory responses and angiogenesis. POMC gene delivery may offer novel therapeutic approach for treating OA.
前阿黑皮素原（POMC）是各种神经肽的前体。POMC 衍生的神经肽是有效的炎症抑制剂和免疫抑制剂。越来越多的证据表明骨关节炎（OA）是一种炎症性疾病。我们评估了 POMC 的关节内基因传递是否可以改善大鼠模型中的实验性诱导 OA。通过在前肢后肢的膝关节中切断前交叉韧带（ACLT），在 Wistar 大鼠中诱导 OA。在 ACLT 后，将编码人 POMC（AdPOMC）的腺病毒载体关节内注射到膝关节中。使用免疫印迹，免疫组织化学和酶联免疫吸附测定评估转基因表达和炎症反应。用组织学方法评估治疗关节的疾病表现。关节内注射后，人 POMC 在软骨细胞和滑膜中表达。POMC 基因转移降低了 HTB-94 软骨肉瘤细胞和 Raw 264.7 巨噬细胞中核因子-κB 活性和白细胞介素-1β的水平；它还降低了滑膜中的微血管密度。组织学检查显示，AdPOMC 治疗大鼠的 OA 症状比用空腺病毒载体（AdNull）或生理盐水治疗的大鼠的症状要轻。关节内注射表达 POMC 的腺病毒载体可显著抑制 OA 的进展和严重程度，并减轻炎症反应和血管生成。POMC 基因传递可能为治疗 OA 提供新的治疗方法。
