Overexpression of heme oxygenase-1 increases human osteoblast stem cell differentiation.
Overexpression of heme oxygenase-1 increases human osteoblast stem cell differentiation.
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DOI：
10.1007/s00774-009-0134-y
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发表时间：
2010-05
影响因子：
3.3
通讯作者：
Asprinio, David
中科院分区：
文献类型：
--
作者：
Barbagallo, Ignazio;Vanella, Angelo;Peterson, Stephen J.;Kim, Dong Hyun;Tibullo, Daniele;Giallongo, Cesarina;Vanella, Luca;Parrinello, Nunziatina;Palumbo, Giuseppe A.;Di Raimondo, Francesco;Abraham, Nader G.;Asprinio, David
人骨髓间充质干细胞 (MSC) 是多效细胞，由于血红素加氧酶 (HO)-1/-2 表达等特定信号通路的串扰，可分化为脂肪细胞或成骨细胞。我们研究了 HO-1 表达诱导剂和 HO 活性抑制剂对 MSC 分化为成骨细胞以及高葡萄糖暴露后的影响。在成骨培养基中培养的 MSC 增加了骨连接蛋白、Runt 相关转录因子 2 (RUNX-2)、骨钙素和碱性磷酸酶的表达。 HO-1表达在分化过程中最初下降，然后在培养15天后反弹增加。此外，HO-1 对成骨细胞的影响似乎与对脂肪细胞干细胞的影响不同。添加钴化合物后，HO-1 的诱导会减少脂肪生成。此外，葡萄糖 (30 mM) 抑制成骨细胞分化，骨形态发生蛋白 (BMP)-2、骨连接蛋白、骨钙蛋白和骨保护素 (OPG) 降低证明了这一点。相比之下，间充质干细胞衍生的脂肪细胞因葡萄糖而增加。 HO-1 表达增加会增加骨连接蛋白、OPG 和 BMP-2 的水平。抑制 H2O2 活性可防止暴露于高葡萄糖水平的细胞中骨连接蛋白的增加，并加剧骨钙素和 OPG 的减少。此外，靶向 HO-1 表达可增加 pAMPK 和内皮一氧化氮合酶 (eNOS)，并恢复成骨细胞标志物。我们的研究结果表明，靶向 HO-1 基因表达可以减轻高血糖介导的 MSC 衍生的成骨细胞分化的降低。最后，HO-1 特异性细胞对成骨细胞和脂肪细胞作用的机制仍有待探索。因此，HO-1基因表达的靶向为增加成骨细胞功能和分化以及通过促进骨形成减轻骨质疏松症提供了途径。
Human bone marrow mesenchymal stem cells (MSCs) are pleiotrophic cells that differentiate to either adipocytes or osteoblasts as a result of crosstalk by specific signaling pathways including heme oxygenase (HO)-1/-2 expression. We examined the effect of inducers of HO-1 expression and inhibitors of HO activity on MSC differentiation to the osteoblast and following high glucose exposure. MSC cultured in osteogenic medium increased expression of osteonectin, Runt-related transcription factor 2 (RUNX-2), osteocalcin, and alkaline phosphatase. HO-1 expression during differentiation was initially decreased and then followed by a rebound increase after 15 days of culture. Additionally, the effect of HO-1 on osteoblasts appears different to that seen in adipocyte stem cells. On addition of a cobalt compound, the resultant induction of HO-1 decreases adipogenesis. Moreover, glucose (30 mM) inhibited osteoblast differentiation, as evidenced by decreased bone morphogenetic protein (BMP)-2, osteonectin, osteocalcin, and osteoprotegerin (OPG). In contrast, MSC-derived adipocytes were increased by glucose. Increased HO-1 expression increased the levels of osteonectin, OPG, and BMP-2. Inhibition of HO activity prevented the increase in osteonectin and potentiated the decrease of osteocalcin and OPG in cells exposed to high glucose levels. Furthermore, targeting HO-1 expression increased pAMPK and endothelial nitric oxide synthase (eNOS) and restored osteoblastic markers. Our findings suggest that targeting HO-1 gene expression attenuates the hyperglycemia-mediated decrease in MSC-derived osteoblast differentiation. Finally, the mechanism underlying the HO-1-specific cell effect on osteoblasts and adipocytes is yet to be explored. Thus, the targeting of HO-1 gene expression presents a portal to increase osteoblast function and differentiation and attenuate osteoporosis by promoting bone formation.
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影响因子：
4.2
作者：
Barbagallo, Ignazio;Tibullo, Daniele;Motterlini, Roberto
通讯作者：
Motterlini, Roberto
影响因子：
4.1
作者：
Chang, SH;Garcia, J;Agarwal, A
通讯作者：
Agarwal, A
影响因子：
3.5
作者：
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影响因子：
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作者：
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Graves, DT
影响因子：
3.4
作者：
Achemlal, L;Tellal, S;El Maghraoui, A
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El Maghraoui, A