Effects induced by BMPS in cultures of human articular chondrocytes: comparative studies.
We compared anabolic and anti-catabolic activities of selected bone morphogenetic proteins (BMP-2, -4, -6, and -7) and cartilage-derived morphogenetic proteins (CDMP-1 and -2) in human normal adult articular chondrocytes. Ankle chondrocytes were cultured in alginate beads in the presence of 10% serum and treated with either growth factors only (each at 100 ng/ml) or the combination of interleukin-1 (IL-1 beta) (0.1 ng/ml) and BMPs. Chondrocyte metabolism was assessed by proteoglycan (PG) synthesis, content, DNA content, and cell survival. The results showed that BMP-2, -4, and -7 were more potent in stimulating PGs than other growth factors tested. The highest levels of PG synthesis were detected at day 9 in the presence of BMP-7. With regard to anti-catabolic properties, the effect depended upon treatment scheme (simultaneous or sequential). Under simultaneous cultures, BMP-2, -4, and -6 failed to counteract IL-1 beta induced inhibition of PG synthesis, while the CDMPs restored this parameter to serum control levels. Only BMP-7 showed consistent and pronounced anti-catabolic activity in either culture treatment scheme. None of the factors induced cell death or chondrocyte proliferation. In conclusion, the growth factors tested showed different levels of effects on human chondrocytes in culture, but only BMP-7 displayed both strong anabolic and anti-catabolic properties.
Chubinskaya
Susan
S
Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA. schubins@rush.edu
Segalite
Diane
D
Pikovsky
Dmitriy
D
Hakimiyan
Arnavaz A
AA
Rueger
David C
DC
D000368:Aged; D000369:Aged, 80 and over; D000464:Alginates; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004357:Drug Synergism; D020723:Glucuronic Acid; D055428:Growth Differentiation Factor 5 / Q000494:pharmacology; D006603:Hexuronic Acids; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D008875:Middle Aged; D011509:Proteoglycans / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D000464:Alginates; D019485:Bone Morphogenetic Proteins; D055428:Growth Differentiation Factor 5; D006603:Hexuronic Acids; D053583:Interleukin-1beta; D011509:Proteoglycans; D011994:Recombinant Proteins; D020723:Glucuronic Acid