Carmeliet G, Nys G, Bouillon R
Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Katholieke Universiteit Leuven, Gasthuisberg, Belgium.
J Bone Miner Res. 1997 May;12(5):786-94. doi: 10.1359/jbmr.1997.12.5.786.
Spaceflight leads to osteopenia in both humans and animals, principally as a result of decreased bone formation, which might be the consequence of impaired osteoblast differentiation. The effect of microgravity on osteoblast differentiation in vitro was investigated using the human osteosarcoma cell line MG-63. Genes related to matrix formation and maturation were quantified both at the protein and mRNA level in untreated and hormone-treated (dihydroxyvitamin D3 [1,25(OH)2D3], 10(-7) M; transforming growth factor beta2 (TGF-beta2), 10 ng/ml) cells cultured for 9 days under microgravity conditions aboard the Foton 10 satellite and compared with ground and inflight unit-gravity cultures. The expression of alkaline phosphatase (ALP) activity following treatment at microgravity increased only by a factor of 1.8 compared with the 3.8-fold increase at unit-gravity (p < 0.01), whereas no alteration was detected in the production of collagen type I between unit- and microgravity. In addition, gene expression for collagen Ialpha1, ALP, and osteocalcin following treatment at microgravity was reduced to 51, 62, and 19%, respectively, of unit-gravity levels (p < 0.02). The lack of correlation between collagen type I gene and protein expression induced by microgravity is most likely related to the different kinetics of gene and protein expression observed at unit-gravity: following treatment with 1,25(OH)2D3 and TGF-beta2, collagen Ialpha1 mRNA increased gradually during 72 h, but collagen type I production was already maximal after treatment for 48 h. In conclusion, microgravity decreases the activity of osteoblasts in vitro; in particular the differentiation of osteoblasts in response to systemic hormones and growth factors is reduced by microgravity.
太空飞行会导致人类和动物出现骨质减少,主要原因是骨形成减少,这可能是成骨细胞分化受损的结果。利用人骨肉瘤细胞系MG-63研究了微重力对体外成骨细胞分化的影响。在“光子10号”卫星上的微重力条件下培养9天的未处理和激素处理(二羟基维生素D3 [1,25(OH)2D3],10(-7) M;转化生长因子β2 (TGF-β2),10 ng/ml)的细胞中,对与基质形成和成熟相关的基因在蛋白质和mRNA水平进行了定量,并与地面和飞行中的单位重力培养物进行了比较。与单位重力下3.8倍的增加相比,微重力处理后碱性磷酸酶(ALP)活性仅增加了1.8倍(p < 0.01),而单位重力和微重力下I型胶原蛋白的产生没有检测到变化。此外,微重力处理后I型胶原蛋白α1、ALP和骨钙素的基因表达分别降至单位重力水平的51%、62%和19%(p < 0.02)。微重力诱导的I型胶原蛋白基因与蛋白质表达之间缺乏相关性很可能与单位重力下观察到的基因和蛋白质表达的不同动力学有关:用1,25(OH)2D3和TGF-β2处理后,I型胶原蛋白α1 mRNA在72小时内逐渐增加,但I型胶原蛋白的产生在处理48小时后已经达到最大值。总之,微重力会降低体外成骨细胞的活性;特别是微重力会降低成骨细胞对全身激素和生长因子的反应性分化。