title: Altered cell metabolism in tissues of the knee joint in a rabbit model of Botulinum toxin A-induced quadriceps muscle weakness.
abstract: 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.
authors.affiliation: Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Alberta, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Leumann
authors.forename: D
authors.initials: D
authors.lastname: Longino
authors.forename: R
authors.initials: R
authors.lastname: Fortuna
authors.forename: T
authors.initials: T
authors.lastname: Leonard
authors.forename: M A
authors.initials: MA
authors.lastname: Vaz
authors.forename: D A
authors.initials: DA
authors.lastname: Hart
authors.forename: W
authors.initials: W
authors.lastname: Herzog
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D058578:Biglycan / Q000235:genetics; D019274:Botulinum Toxins, Type A; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D017885:Collateral Ligaments / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D007719:Knee Joint / Q000378:metabolism* / Q000503:physiopathology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D017888:Medial Collateral Ligament, Knee / Q000378:metabolism; D008592:Menisci, Tibial / Q000378:metabolism; D018908:Muscle Weakness / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D009929:Organ Size; D017847:Patellar Ligament / Q000378:metabolism; D052097:Quadriceps Muscle / Q000473:pathology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D058578:Biglycan; D024042:Collagen Type I; D024061:Collagen Type III; D007375:Interleukin-1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D019274:Botulinum Toxins, Type A; D020781:Matrix Metalloproteinase 1