Differential effects of bone morphogenetic protein-2 and transforming growth factor-β1 on gene expression of collagen-modifying enzymes in human adipose tissue-derived mesenchymal stem cells

摘要

Adipose tissue-derived mesenchymal stem cells (AT-MSCs) in combination with bone morphogenetic protein-2 (BMP-2) or transforming growth factor-β1 (TGF-β1) are under evaluation for bone tissue engineering. Posttranslational modification of type I collagen is essential for functional bone tissue with adequate physical and mechanical properties. We investigated whether BMP-2 (10-100ng/mL) and/or TGF-β1 (1-10ng/mL) affect gene expression of α2(I) procollagen and collagen-modifying enzymes, that is, lysyl oxidase and lysyl hydroxylases 1, 2, and 3 (encoded by PLOD1, 2, and 3), by human AT-MSCs. BMP-2, but not TGF-β1, increased alkaline phosphatase activity after 28 days, indicating osteogenic differentiation of AT-MSCs. At day 4, both BMP-2 and TGF-β1 upregulated α2(I) procollagen and PLOD1, which was downregulated at day 28. TGF-β1, but not BMP-2, downregulated PLOD3 at day 28. Lysyl oxidase was upregulated by TGF-β1 at day 4 and by BMP-2 at day 7. Neither BMP-2 nor TGF-β1 affected PLOD2. In conclusion, these results suggest that AT-MSCs differentially respond to BMP-2 and TGF-β1 with changes in gene expression of collagen-modifying enzymes. AT-MSCs may thus be able to appropriately modify type I collagen to form a functional bone extracellular matrix for tissue engineering, dependent on the growth factor added.