Knee muscle atrophy is a risk factor for development of knee osteoarthritis in a rat model

Abstract

OBJECTIVES: 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. METHODS: 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]}. RESULTS: 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. CONCLUSIONS: Quadriceps muscle atrophy triggered the subchondral bone abnormal change and cartilage degeneration, which would be a risk factor for development of osteoarthritis. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our results indicate that anti-quadriceps muscle atrophy can be a candidate therapeutic target in the prevention of knee osteoarthritis.