Knippenberg M, Helder M N, de Blieck-Hogervorst J M A, Wuisman P I J M, Klein-Nulend J
Department of Oral Cell Biology, Academic Center of Dentistry Amsterdam (ACTA)-Universiteit van Amsterdam and Vrije Universiteit, Research Institute MOVE, Amsterdam, The Netherlands.
Tissue Eng. 2007 Oct;13(10):2495-503. doi: 10.1089/ten.2006.0420.
Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are currently used for bone tissue engineering. AT-MSCs undergoing osteogenic differentiation respond to mechanical loading with increased cyclooxygenase-2 gene expression, a key enzyme in prostaglandin (PG) synthesis. PGs are potent multifunctional regulators in bone, exhibiting stimulatory and inhibitory effects on bone formation and resorption. PGE(2), but not PGI(2) or PGF(2), recruits osteoprogenitors from the bone marrow space and influences their differentiation. We hypothesize that PGE(2), PGI(2), and PGF(2) may differentially regulate osteogenic differentiation of human AT-MSCs. PGE(2), PGI(2), and PGF(2) (0.01-10 microM) affected osteogenic differentiation, but not proliferation of AT-MSCs after 4-14 days. Only PGF(2) (0.01-10 microM) increased alkaline phosphatase (ALP) activity at day 4. PGE(2) (10 microM), PGI(2) (0.01-10 microM), and PGF(2) (10 microM) decreased ALP activity, whereas PGF(2) (0.1 microM) increased ALP activity at day 14. PGF(2) (0.01-0.1 microM) and PGI(2) (0.01 microM) upregulated osteopontin gene expression, and PGF(2) (0.01 microM) upregulated alpha1(I)procollagen gene expression at day 4. PGE(2) and PGF(2) (10 microM) at day 4 and PGF(2) (1 microM) at day 14 downregulated runt-related transcription factor-2 gene expression. We conclude that PGE(2), PGI(2), and PGF(2) differentially affect osteogenic differentiation of AT-MSCs, with PGF(2) being the most potent. Thus, locally produced PGF(2) might be most beneficial in promoting osteogenic differentiation of AT-MSCs, resulting in enhanced bone formation for bone tissue engineering.
脂肪组织来源的间充质干细胞（AT-MSCs）目前被用于骨组织工程。经历成骨分化的AT-MSCs对机械负荷产生反应，伴随着环氧化酶-2基因表达增加，环氧化酶-2是前列腺素（PG）合成中的关键酶。PGs是骨中强大的多功能调节因子，对骨形成和吸收表现出刺激和抑制作用。前列腺素E2（PGE2），而非前列环素（PGI2）或前列腺素F2α（PGF2），从骨髓腔募集骨祖细胞并影响其分化。我们假设PGE2、PGI2和PGF2可能对人AT-MSCs的成骨分化有不同的调节作用。4至14天后，PGE2、PGI2和PGF2（0.01 - 10微摩尔）影响AT-MSCs的成骨分化，但不影响其增殖。仅PGF2（0.01 - 10微摩尔）在第4天增加碱性磷酸酶（ALP）活性。PGE2（10微摩尔）、PGI2（0.01 - 10微摩尔）和PGF2（10微摩尔）在第4天降低ALP活性，而PGF2（0.1微摩尔）在第14天增加ALP活性。PGF2（0.01 - 0.1微摩尔）和PGI2（0.01微摩尔）在第4天上调骨桥蛋白基因表达，PGF2（0.01微摩尔）在第4天上调α1（I）前胶原基因表达。第4天的PGE2和PGF2（10微摩尔）以及第14天的PGF2（1微摩尔）下调矮小相关转录因子-2基因表达。我们得出结论，PGE2、PGI2和PGF2对AT-MSCs的成骨分化有不同影响，其中PGF2作用最强。因此，局部产生的PGF2可能对促进AT-MSCs的成骨分化最有益，从而增强骨组织工程中的骨形成。
