Xu Jichun, She Guorong, Gui Tao, Hou Huige, Li Jieruo, Chen Yuanfeng, Zha Zhengang
Institute of Orthopedic Diseases and Center for Joint Surgery and Sports Medicine, The First Affiliated Hospital, Jinan University, Guangzhou, PR China.
J Orthop Translat. 2019 Nov 1;22:67-72. doi: 10.1016/j.jot.2019.10.003. eCollection 2020 May.
The objective of this study was to investigate the effect of botulinum toxin type A (BTX-A)-induced quadriceps muscle atrophy on the cartilage and subchondral bone in an otherwise intact rat joint model.
The rat right quadriceps muscle atrophy was established by intramuscular injection of BTX-A. Twenty-four rats were divided randomly into 3 groups: The BTX-A-treated 4-week group; the BTX-A-treated 8-week group; and the control group injected with phosphate buffer saline were observed for 8 weeks. Muscle atrophy level was measured by weighing and histology examinations. Serum interleukin-1β level was tested by ELISA (enzyme linked immunosorbent assay); the subchondral bone was analysed by micro-computed tomography and the cartilage was measured by histology examinations (gross view, haematoxylin and eosin staining and Safranin-O/fast green staining) and immunohistochemistry test {collagen X [ColX]}.
BTX-A intramuscular injection led to muscle atrophy. Characteristics of muscle atrophy appeared in two BTX-A-injected groups but not in the control group. Quadriceps atrophy did not affect interleukin-1β level in serum, but resulted in subchondral bone abnormal changes with reduced bone volume/total tissue volume and increased Structure Model Index. Furthermore, the more the severe cartilage damage, the higher the histologic damage scores, followed by the higher the percentage of collagen X-positive chondrocytes caused by muscle atrophy.
Quadriceps muscle atrophy triggered the subchondral bone abnormal change and cartilage degeneration, which would be a risk factor for development of osteoarthritis.
Our results indicate that anti-quadriceps muscle atrophy can be a candidate therapeutic target in the prevention of knee osteoarthritis.
本研究的目的是在其他方面均完整的大鼠关节模型中,研究A型肉毒杆菌毒素(BTX-A)诱导的股四头肌萎缩对软骨和软骨下骨的影响。
通过肌肉注射BTX-A建立大鼠右股四头肌萎缩模型。将24只大鼠随机分为3组:BTX-A治疗4周组;BTX-A治疗8周组;注射磷酸盐缓冲盐水的对照组,观察8周。通过称重和组织学检查测量肌肉萎缩程度。采用酶联免疫吸附测定法(ELISA)检测血清白细胞介素-1β水平;通过微型计算机断层扫描分析软骨下骨,通过组织学检查(大体观察、苏木精和伊红染色以及番红O/固绿染色)和免疫组织化学检测{X型胶原[ColX]}测量软骨。
肌肉注射BTX-A导致肌肉萎缩。两个注射BTX-A的组出现了肌肉萎缩特征,而对照组未出现。股四头肌萎缩不影响血清白细胞介素-1β水平,但导致软骨下骨出现异常变化,骨体积/总体积降低,结构模型指数增加。此外,软骨损伤越严重,组织学损伤评分越高,随后肌肉萎缩导致的X型胶原阳性软骨细胞百分比越高。
股四头肌萎缩引发软骨下骨异常变化和软骨退变,这可能是骨关节炎发生发展的一个危险因素。
我们的结果表明,抗股四头肌萎缩可能是预防膝关节骨关节炎的一个候选治疗靶点。