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Altered cell metabolism in tissues of the knee joint in a rabbit model of Botulinum toxin A-induced quadriceps muscle weakness


Corresponding author: Walter Herzog, PhD, Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4. Tel: +403 220 8525, Fax: +403 284 3553, E-mail:


Quadriceps muscle weakness is frequently associated with knee injuries in sports. The influence of quadriceps weakness on knee joint homeostasis remains undefined. We hypothesized that quadriceps weakness will lead to tissue-specific alterations in the cell metabolism of tissues of the knee. Quadriceps weakness was induced with repetitive injections of Botulinum toxin A in six 1-year-old New Zealand White rabbits for 6 months. Five additional animals served as controls with injections of saline/dextrose. Muscle weakness was assessed by muscle wet mass, isometric knee extensor torque, and histological morphology analysis. Cell metabolism was assessed for patellar tendon, medial and lateral collateral ligament, and medial and lateral meniscus by measuring the total RNA levels and specific mRNA levels for collagen I, collagen III, MMP-1, MMP-3, MMP-13, TGF-β, biglycan, IL-1, and bFGF by reverse transcription and polymerase chain reaction. While the total RNA levels did not change, tissue-specific mRNA levels were lower for relevant anabolic and catabolic molecules, indicating potential changes in tissue mechanical set points. Quadriceps weakness may lead to adaptations in knee joint tissue cell metabolism by altering a subset of anabolic and catabolic mRNA levels corresponding to a new functional and metabolic set point for the knee that may contribute to the high injury rate of athletes with muscle weakness.