Department of Orthopaedic Surgery, Zhongnan Hospital, Wuhan University, Wuhan, China.
Exp Mol Med. 2010 Oct 31;42(10):684-95. doi: 10.3858/emm.2010.42.10.067.
The study investigated the effects of adenovirus-mediated gene transfection of basic fibroblast growth factor (bFGF), bFGF combined with interleukin-1 receptor antagonist protein (IL-Ra) and/or insulin-like growth factor-1 (IGF-1) both in human osteoarthritis (OA) chondrocytes and rabbits OA model. Human OA chondrocytes were delivered by adenovirus-mediated bFGF, IL-Ra and IGF-1 vectors, respectively. Chondrocyte proliferation, glycosaminoglycan (GAG) content, expression of type II collagen, ADAMTS-5, MMP-13, MMP-3 and TIMP-1 were determined. Rabbit OA model was induced by anterior cruciate ligament transaction (ACLT) in knees. Adenoviral vectors encoding human bFGF, IL-Ra and IGF-1 were injected intraarticularly into the knee joints after ACLT. The effects of adenovirus-mediated gene transfection on rabbit OA were evaluated. In vitro, the transfected genes were expressed in cell supernatant of human OA chondrocytes. AdbFGF group significantly promoted chondrocyte proliferation, and increased GAG and type II collagen synthesis than in the OA group. As two or three genes were transfected in different combinations, there was significant enhancement on the GAG content, type II collagen synthesis, and TIMP-1 levels, while ADAMTS-5, MMP-13, and MMP-3 levels were reduced. In vivo, the transfected genes were expressed in synovial fluid of rabbits. Intraarticular delivery of bFGF enhanced the expression of type II collagen in cartilage and decreased cartilage Mankin score compared with the OA control group (P=0.047; P<0.01, respectively). Multiple-gene transfection in different combinations showed better results than bFGF transfection alone. This study suggests that bFGF gene transfection is effective in treating experimental OA. Multiple gene transfection has better biologic effects on OA.
该研究调查了腺病毒介导的碱性成纤维细胞生长因子(bFGF)基因转染、bFGF 联合白细胞介素-1 受体拮抗剂蛋白(IL-Ra)和/或胰岛素样生长因子-1(IGF-1)在人骨关节炎(OA)软骨细胞和兔 OA 模型中的作用。分别通过腺病毒介导的 bFGF、IL-Ra 和 IGF-1 载体转染人 OA 软骨细胞。测定软骨细胞增殖、糖胺聚糖(GAG)含量、II 型胶原、ADAMTS-5、MMP-13、MMP-3 和 TIMP-1 的表达。通过膝关节前交叉韧带切断术(ACLT)诱导兔 OA 模型。在 ACLT 后,将编码人 bFGF、IL-Ra 和 IGF-1 的腺病毒载体关节内注射到膝关节中。评估腺病毒介导的基因转染对兔 OA 的影响。在体外,转染基因在人 OA 软骨细胞的细胞上清液中表达。与 OA 组相比,AdbFGF 组显著促进软骨细胞增殖,并增加 GAG 和 II 型胶原合成。当两种或三种基因以不同组合转染时,GAG 含量、II 型胶原合成和 TIMP-1 水平显著增强,而 ADAMTS-5、MMP-13 和 MMP-3 水平降低。在体内,转染基因在兔的滑液中表达。与 OA 对照组相比,关节内给予 bFGF 可增强软骨中 II 型胶原的表达,降低软骨 Mankin 评分(P=0.047;P<0.01)。不同组合的多基因转染比 bFGF 转染单独显示出更好的效果。本研究表明,bFGF 基因转染可有效治疗实验性 OA。多基因转染对 OA 具有更好的生物学作用。