BMP-7 protects against progression of cartilage degeneration after impact injury.
In vivo studies were used to characterize a model of cartilage injury leading to osteoarthritis progression in the medial femorotibial joint of sheep. In three subsequent studies, bilateral impact injuries were created and one joint received intraarticular injections of 340 microg of rhBMP-7 protein in a collagen particle carrier while the contralateral knee received the vehicle alone. Sheep were allocated to three groups that received intraarticular injections on day 0 (group A), 21 (group B), or 90 (group C) after experimental knee injury. In each group the, joints were evaluated for signs of osteoarthritis progression 90 days after the last treatment using India ink stained area, OARSI histological scoring, cartilage sGAG content, immunostaining for apoptosis (TUNEL), caspase-3, collagen degradation (Col 2 3/4C short collagen epitope), and the endogenous (pro-) form of BMP-7 protein. Knee joints that received rhBMP-7 immediately after injury had small focal lesions at the injury site that did not progress into the surrounding cartilage. Joints that received BMP-7 3 weeks after injury were improved and had limited progression compared to controls, but joints that received the protein 12 weeks after injury had no statistically significant improvement. These studies suggest that BMP-7 may be chondroprotective after traumatic injury in patients if it is administered within 3 to 4 weeks of the index injury. The mechanism of protection after sublethal injury appeared to be an increased survival of chondrocytes that are able to participate in the repair process.
Hurtig
Mark
M
Department of Clinical Studies, University of Guelph, 50 McGilvray Lane, Guelph, ON, Canada, N1G 2W1. mhurtig@uoguelph.ca
Chubinskaya
Susan
S
Dickey
Jim
J
Rueger
David
D
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000473:pathology; D019485:Bone Morphogenetic Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002358:Cartilage, Articular / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000293:injuries; D006614:Hindlimb / Q000293:injuries; D006801:Humans; D020287:In Situ Nick-End Labeling; D007270:Injections, Intra-Articular; D007596:Joints / Q000293:injuries; D007718:Knee Injuries / Q000188:drug therapy / Q000473:pathology*; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology
D019485:Bone Morphogenetic Proteins; C511401:osteogenic protein 1 putty, recombinant human