title: In vivo assessment of macromolecular content in articular cartilage of the goat knee.
abstract: Loss of proteoglycans (PGs) from the extracellular matrix of cartilage is an early event of osteoarthritis. The capability of Gd(DTPA)(2-)-enhanced MRI to quantitatively assess PG content was explored in a goat model of cartilage degeneration. Partial to total PG depletion was induced by an intraarticular injection of papain 1 day prior to the MRI session. A close correlation was found between the extent of the PG loss and the Gd(DTPA)(2-)-induced T(1) decrease. Papain-induced PG depletion was confirmed by post-mortem histological and biochemical assessments. A 2-hr delay after Gd(DTPA)(2-) injection was found to be optimal for an accurate quantitation of the cartilage defect. A series of knee flexions were performed post-Gd(DTPA)(2-) injection to facilitate penetration of the contrast agent into cartilage. However, DeltaT(1)'s observed in cartilage of exercised goat knees were not affected by papain or IL1beta pretreatment. Therefore, as long as a preinjection T(1) map was obtained, the Gd(DTPA)(2-)-enhanced MRI technique provided good sensitivity in detecting partial loss of PG in articular cartilage. This was true only when the animal was maintained in a resting state during diffusion of the Gd(DTPA)(2-). This approach is of particular interest for long-term evaluations of cartilage degeneration and regeneration.
authors.affiliation: Novartis Institute for Biomedical Research, East Hanover, New Jersey 07936, USA. didier.laurent@pharma.novartis.com
authors.forename: Didier
authors.initials: D
authors.lastname: Laurent
authors.forename: James
authors.initials: J
authors.lastname: Wasvary
authors.forename: Markus
authors.initials: M
authors.lastname: Rudin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: O'Byrne
authors.forename: Theodore
authors.initials: T
authors.lastname: Pellas
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D003287:Contrast Media; D004195:Disease Models, Animal; D005260:Female; D019786:Gadolinium DTPA; D006041:Goats; D008279:Magnetic Resonance Imaging; D010003:Osteoarthritis / Q000139:chemically induced / Q000175:diagnosis*; D010206:Papain; D011509:Proteoglycans / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D011509:Proteoglycans; D010206:Papain; D019786:Gadolinium DTPA