Periodic knee injections of BMP-7 delay cartilage degeneration induced by excessive running in rats.
Strenuous running of rats enhances mechanical stress on the knee, thereby inducing degeneration of articular cartilage. Bone morphogenetic protein-7 (BMP-7) has an inhibitory effect on cartilage degeneration, suggesting its usefulness for human osteoarthritis patients. However, its mode of administration should be investigated. We examined whether weekly knee injections of BMP-7 delayed the progression of cartilage degeneration. Wistar rats were forced to run 30 km in 6 weeks on a rodent treadmill, and BMP-7 was injected weekly into the knee. Macroscopically and histologically, this strenuous running regimen induced cartilage degeneration. Weekly injections of 250 ng BMP-7 delayed the progression of cartilage degeneration. Immunohistochemically, in the control knee, type II collagen expression decreased, while BMP-7 expression in chondrocytes slightly increased. Interestingly, weekly injection of BMP-7 increased BMP-7 expression even 9 days after the final injection. Disulfate disaccharide keratan sulfate in serum transiently increased in the control group, while it remained at a low level in the BMP-7 group. Weekly BMP-7 injection increased BMP-7 expression in chondrocytes and its effect seemed to last more than 7 days. The effect of BMP-7 could be monitored by serum keratan sulfate concentration. Periodical injections of BMP-7 delayed progression of cartilage degeneration induced by excessive running in rats.
Sekiya
Ichiro
I
Section of Cartilage Regeneration, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. sekiya.orj@tmd.ac.jp
Tang
Tao
T
Hayashi
Masaya
M
Morito
Toshiyuki
T
Ju
Young-Jin
YJ
Mochizuki
Tomoyuki
T
Muneta
Takeshi
T
D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000096:biosynthesis / Q000627:therapeutic use*; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology*; D019902:Chondrocytes / Q000378:metabolism; D024043:Collagen Type II / Q000096:biosynthesis; D007270:Injections, Intra-Articular; D007632:Keratan Sulfate / Q000378:metabolism; D007719:Knee Joint / Q000473:pathology; D010003:Osteoarthritis / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D012420:Running / Q000293:injuries
D055419:Bone Morphogenetic Protein 7; D024043:Collagen Type II; D007632:Keratan Sulfate