外源性成纤维细胞生长因子9可减轻创伤后骨关节炎中的软骨降解并加重骨赘形成。
Exogenous fibroblast growth factor 9 attenuates cartilage degradation and aggravates osteophyte formation in post-traumatic osteoarthritis.
作者信息
Zhou S, Wang Z, Tang J, Li W, Huang J, Xu W, Luo F, Xu M, Wang J, Wen X, Chen L, Chen H, Su N, Shen Y, Du X, Xie Y, Chen L
机构信息
Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Department of Military Nursing, School of Nursing, Third Military Medical University, Chongqing 400042, China.
出版信息
Osteoarthritis Cartilage. 2016 Dec;24(12):2181-2192. doi: 10.1016/j.joca.2016.07.005. Epub 2016 Jul 27.
OBJECTIVE
The aim of the present study is to investigate the effects of exogenous fibroblast growth factor (FGF)9 on the progression of post-traumatic osteoarthritis (OA).
DESIGN
The expression of FGF9 in articular cartilage with OA is detected by immunohistochemistry (IHC). The effects of intra-articular exogenous FGF9 injection on post-traumatic OA induced by the destabilization of the medial meniscus (DMM) surgery are evaluated. Cartilage changes and osteophyte formation in knee joints are investigated by histological analysis. Changes in subchondral bone are evaluated by microcomputed tomography (micro-CT). The effect of exogenous FGF9 on an interleukin-1β (IL-1β)-induced ex vivo OA model of human articular cartilage tissues is also evaluated.
RESULTS
FGF9 expression was down-regulated in articular chondrocytes of OA but ectopically induced at sites of osteophyte formation. Intra-articular injection of exogenous FGF9 attenuated articular cartilage degradation in mice after DMM surgery. Exogenous FGF9 suppressed collagen X and MMP13 expressions in OA cartilage, while promoted collagen II expression. Similar results were observed in IL-1β-induced ex vivo OA model. Intra-articular injection of FGF9 had no significant effect on the subchondral bone of knee joints after DMM surgery, but aggravated osteophyte formation. The expressions of SOX9 and collagen II, and cell proliferation were up-regulated at sites of initial osteophyte formation in mice with exogenous FGF9 treatment.
CONCLUSIONS
Intra-articular injection of exogenous FGF9 delays articular cartilage degradation in post-traumatic OA, while aggravates osteophyte formation.
目的
本研究旨在探讨外源性成纤维细胞生长因子（FGF）9对创伤后骨关节炎（OA）进展的影响。
设计
采用免疫组织化学（IHC）检测OA关节软骨中FGF9的表达。评估关节腔内注射外源性FGF9对内侧半月板不稳定（DMM）手术诱导的创伤后OA的影响。通过组织学分析研究膝关节软骨变化和骨赘形成。采用微型计算机断层扫描（micro-CT）评估软骨下骨的变化。还评估了外源性FGF9对白细胞介素-1β（IL-1β）诱导的人关节软骨组织体外OA模型的影响。
结果
OA关节软骨细胞中FGF9表达下调，但在骨赘形成部位异位诱导表达。关节腔内注射外源性FGF9可减轻DMM手术后小鼠的关节软骨降解。外源性FGF9抑制OA软骨中胶原蛋白X和基质金属蛋白酶13的表达，同时促进胶原蛋白II的表达。在IL-1β诱导的体外OA模型中也观察到类似结果。关节腔内注射FGF9对DMM手术后膝关节软骨下骨无显著影响，但加重了骨赘形成。外源性FGF9处理的小鼠初始骨赘形成部位的SOX9和胶原蛋白II表达以及细胞增殖上调。
结论
关节腔内注射外源性FGF9可延缓创伤后OA的关节软骨降解，但会加重骨赘形成。
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