title: Context-specific protection of TGFα null mice from osteoarthritis.
abstract: Transforming growth factor alpha (TGFα) is a growth factor involved in osteoarthritis (OA). TGFα induces an OA-like phenotype in articular chondrocytes, by inhibiting matrix synthesis and promoting catabolic factor expression. To better understand TGFα's potential as a therapeutic target, we employed two in vivo OA models: (1) post-traumatic and (2) aging related OA. Ten-week old and six-month old male Tgfa null mice and their heterozygous (control) littermates underwent destabilization of the medial meniscus (DMM) surgery. Disease progression was assessed histologically using the Osteoarthritis Research Society International (OARSI) scoring system. As well, spontaneous disease progression was analyzed in eighteen-month-old Tgfa null and heterozygous mice. Ten-week old Tgfa null mice were protected from OA progression at both seven and fourteen weeks post-surgery. No protection was seen however in six-month old null mice after DMM surgery, and no differences were observed between genotypes in the aging model. Thus, young Tgfa null mice are protected from OA progression in the DMM model, while older mice are not. In addition, Tgfa null mice are equally susceptible to spontaneous OA development during aging. Thus, TGFα might be a valuable therapeutic target in some post-traumatic forms of OA, however its role in idiopathic disease is less clear.
authors.affiliation: Department of Physiology &Pharmacology, Schulich School of Medicine &Dentistry, The University of Western Ontario, London, ON, Canada.
authors.forename: Shirine E
authors.initials: SE
authors.lastname: Usmani
authors.affiliation: Department of Physiology &Pharmacology, Schulich School of Medicine &Dentistry, The University of Western Ontario, London, ON, Canada.
authors.forename: Veronica
authors.initials: V
authors.lastname: Ulici
authors.affiliation: Department of Physiology &Pharmacology, Schulich School of Medicine &Dentistry, The University of Western Ontario, London, ON, Canada.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pest
authors.affiliation: Department of Animal Care and Veterinary Services, University of Western Ontario, London, Canada.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Hill
authors.affiliation: Department of Animal Care and Veterinary Services, University of Western Ontario, London, Canada.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Welch
authors.affiliation: Department of Physiology &Pharmacology, Schulich School of Medicine &Dentistry, The University of Western Ontario, London, ON, Canada.
authors.forename: Frank
authors.initials: F
authors.lastname: Beier
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D024043:Collagen Type II / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D000939:Epitopes / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008592:Menisci, Tibial / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000517:prevention & control*; D016211:Transforming Growth Factor alpha / Q000172:deficiency* / Q000378:metabolism; D014947:Wounds and Injuries / Q000473:pathology
chemical_list: D024043:Collagen Type II; D000939:Epitopes; D016211:Transforming Growth Factor alpha; D053509:Matrix Metalloproteinase 13