Chubinskaya Susan, Segalite Diane, Pikovsky Dmitriy, Hakimiyan Arnavaz A, Rueger David C
Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA.
Growth Factors. 2008 Oct;26(5):275-83. doi: 10.1080/08977190802291733.
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.
我们比较了选定的骨形态发生蛋白(BMP-2、-4、-6和-7)以及软骨衍生形态发生蛋白(CDMP-1和-2)在人类正常成年关节软骨细胞中的合成代谢和抗分解代谢活性。将踝关节软骨细胞培养在含有10%血清的藻酸盐珠中,并分别用仅生长因子(每种100 ng/ml)或白细胞介素-1(IL-1β)(0.1 ng/ml)与骨形态发生蛋白的组合进行处理。通过蛋白聚糖(PG)合成、含量、DNA含量和细胞存活来评估软骨细胞代谢。结果表明,BMP-2、-4和-7在刺激PG方面比其他测试生长因子更有效。在BMP-7存在的情况下,第9天检测到最高水平的PG合成。关于抗分解代谢特性,效果取决于处理方案(同时或顺序)。在同时培养的情况下,BMP-2、-4和-6未能抵消IL-1β诱导的PG合成抑制,而软骨衍生形态发生蛋白将该参数恢复到血清对照水平。在任何一种培养处理方案中,只有BMP-7表现出一致且显著的抗分解代谢活性。这些因子均未诱导细胞死亡或软骨细胞增殖。总之,所测试的生长因子对培养中的人类软骨细胞显示出不同程度的影响,但只有BMP-7同时具有强大的合成代谢和抗分解代谢特性。