The activin A-follistatin system: potent regulator of human extracellular matrix mineralization

被引:137
作者
Eijken, Marco
Swagemakers, Sigrid
Koedam, Marijke
Steenbergen, Cobie
Derkx, Pieter
Uitterlinden, Andre G.
van der Spek, Peter J.
Visser, Jenny A.
de Jong, Frank H.
Pols, Huibert A. P.
van Leeuwen, Johannes P. T. M.
机构
[1] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands
[2] Erasmus MC, Dept Bioinformat, Rotterdam, Netherlands
关键词
osteoblasts; vascular smooth muscle cells; microarray; autocrine;
D O I
10.1096/fj.07-8080com
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bone quality is an important determinant of osteoporosis, and proper osteoblast differentiation plays an important role in the control and maintenance of bone quality. We investigated the impact of activin signaling on human osteoblast differentiation, extracellular matrix formation, and mineralization. Activins belong to the transforming growth factor-beta superfamily and activin A treatment strongly inhibited mineralization in osteoblast cultures, whereas the activin antagonist follistatin increased mineralization. Osteoblasts produced activin A and follistatin in a differentiation-dependent manner, leading to autocrine regulation of extracellular matrix formation and mineralization. In addition, mineralization in a vascular smooth muscle cell-based model for pathological calcification was inhibited. Comparative activin A and follistatin gene expression profiling showed that activin signaling changes the expression of a specific range of extracellular matrix proteins prior to the onset of mineralization, leading to a matrix composition with reduced or no mineralizing capacity. These findings demonstrate the regulation of osteoblast differentiation and matrix mineralization by the activin A-follistatin system, providing the possibility to control bone quality as well as pathological calcifications such as atherosclerosis by using activin A, follistatin, or analogs thereof.-Eijken, M., Swagemakers, S., Koedam, M., Steenbergen, C., Derkx, P., Uitterlinden, A. G., van der Spek, P. J., Visser, J. A., de Jong, F. H., Pols, H. A. P., van Leeuwen, J. P. T. M. The activin A- follistatin system: potent regulator of human extracellular matrix mineralization.
引用
收藏
页码:2949 / 2960
页数:12
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