Moore E E, Bendele A M, Thompson D L, Littau A, Waggie K S, Reardon B, Ellsworth J L
ZymoGenetics, Inc., 1201 Eastlake Avenue East, Seattle, WA 98102, USA.
Osteoarthritis Cartilage. 2005 Jul;13(7):623-31. doi: 10.1016/j.joca.2005.03.003.
Osteoarthritis (OA) is the most common form of arthritis and a primary cause of disability, however, there are no treatments that can slow disease progression or repair damaged joint cartilage. Fibroblast growth factor-18 (FGF18) has been reported to have significant anabolic effects on cartilage. We therefore examined its effects on repair of cartilage damage in a rat meniscal tear model of OA.
Surgical damage to the meniscus in rats leads to joint instability and significant damage to the articular cartilage at 3 weeks post-surgery. At this time, animals received bi-weekly intra-articular injections of FGF18 for 3 weeks, and the knee joints were then harvested for histologic examination.
FGF18-induced dose-dependent increases in cartilage thickness of the tibial plateau, due to new cartilage formation at the articular surface and the joint periphery. The generation of new cartilage resulted in significant reductions in cartilage degeneration scores. The highest dose of FGF18 also induced an increase in chondrophyte size and increased remodeling of the subchondral bone.
The results of this study demonstrate that FGF18 can stimulate repair of damaged cartilage in a setting of rapidly progressive OA in rats.
骨关节炎(OA)是最常见的关节炎形式,也是导致残疾的主要原因,然而,目前尚无能够减缓疾病进展或修复受损关节软骨的治疗方法。据报道,成纤维细胞生长因子18(FGF18)对软骨具有显著的合成代谢作用。因此,我们在OA大鼠半月板撕裂模型中研究了其对软骨损伤修复的影响。
大鼠半月板手术损伤会导致术后3周关节不稳定和关节软骨严重损伤。此时,动物每两周接受一次关节内注射FGF18,持续3周,然后取出膝关节进行组织学检查。
FGF18诱导胫骨平台软骨厚度呈剂量依赖性增加,这是由于关节表面和关节周边形成了新的软骨。新软骨的生成导致软骨退变评分显著降低。最高剂量的FGF18还诱导软骨细胞大小增加,并促进软骨下骨的重塑。
本研究结果表明,FGF18可以刺激大鼠快速进展性OA中受损软骨的修复。