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【文摘发布】罗格列酮诱导骨量及骨强度下降可
Author：Oxana P. Lazarenko, Sylwia O. Rzonca, William R. Hogue, Frances L. Swain, Larry J. Suva, and Beata Lecka-Czernik
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Abstract：
Peroxisome proliferator-activated receptor-γ (PPARγ) regulates both glucose metabolism and bone mass. Recent evidence suggests that the therapeutic modulation of PPARγ activity with antidiabetic thiazolidinediones elicits unwanted effects on bone. In this study, the effects of rosiglitazone on the skeleton of growing (1 month), adult (6 month), and aged (24 month) C57BL/6 mice were determined. Aging was identified as a confounding factor for rosiglitazone-induced bone loss that correlated with the increased expression of PPARγ in bone marrow mesenchymal stem cells. The bone of young growing mice was least affected, although a significant decrease in bone formation rate was noted. In both adult and aged animals, bone volume was significantly decreased by rosiglitazone. In adult animals, bone loss correlated with attenuated bone formation, whereas in aged animals, bone loss was associated with increased osteoclastogenesis, mediated by increased receptor activator of nuclear factor-κ B ligand (RANKL) expression. PPARγ activation led to changes in marrow structure and function such as a decrease in osteoblast number, an increase in marrow fat cells, an increase in osteoclast number, and a loss of the multipotential character of marrow mesenchymal stem cells. In conclusion, rosiglitazone induces changes in bone reminiscent of aged bone and appears to induce bone loss by altering the phenotype of marrow mesenchymal stem cells.
PMID: 17332064 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 Title：Rosiglitazone Induces Decreases in Bone Mass and Strength that Are Reminiscent of Aged Bone
题目：罗格列酮可导致类似骨老化的骨密度及骨强度的下降
Author：Oxana P. Lazarenko, Sylwia O. Rzonca, William R. Hogue, Frances L. Swain, Larry J. Suva, and Beata Lecka-Czernik
作者：Oxana P. Lazarenko, Sylwia O. Rzonca, William R. Hogue, Frances L. Swain, Larry J. Suva, and Beata Lecka-Czernik
Resource:
Abstract：
Peroxisome proliferator-activated receptor-γ (PPARγ) regulates both glucose metabolism and bone mass. Recent evidence suggests that the therapeutic modulation of PPARγ activity with antidiabetic thiazolidinediones elicits unwanted effects on bone. In this study, the effects of rosiglitazone on the skeleton of growing (1 month), adult (6 month), and aged (24 month) C57BL/6 mice were determined. Aging was identified as a confounding factor for rosiglitazone-induced bone loss that correlated with the increased expression of PPARγ in bone marrow mesenchymal stem cells. The bone of young growing mice was least affected, although a significant decrease in bone formation rate was noted. In both adult and aged animals, bone volume was significantly decreased by rosiglitazone. In adult animals, bone loss correlated with attenuated bone formation, whereas in aged animals, bone loss was associated with increased osteoclastogenesis, mediated by increased receptor activator of nuclear factor-κ B ligand (RANKL) expression. PPARγ activation led to changes in marrow structure and function such as a decrease in osteoblast number, an increase in marrow fat cells, an increase in osteoclast number, and a loss of the multipotential character of marrow mesenchymal stem cells. In conclusion, rosiglitazone induces changes in bone reminiscent of aged bone and appears to induce bone loss by altering the phenotype of marrow mesenchymal stem cells.
摘要：
过氧化物酶体增殖物激活受体γ(PPARγ)能调节糖代谢和骨密度。最近的证据显示，利用噻唑烷二酮类糖尿病药物（thiazolidinediones）对PPARγ活性进行治疗性的调节能对骨骼产生有害的副作用。在本研究中，我们弄清了罗格列酮（rosiglitazone）对各年龄段的C57BL/6小鼠的骨骼作用进行，包括发育期（1月），成年期（6月）和老年期（24月）三个阶段。老龄化是伴罗格列酮所致骨丢失的混杂因素，在骨丢失过程中伴随了髓间质干细胞PPARγ表达的增加。虽然罗格列酮使年幼的发育期小鼠的骨骼形成速度明显下降， 但是该年龄段受到的影响还是最小。在成年和老年小鼠中，罗格列酮使骨总量明显下降。在成年动物中，骨丢失和骨形成减弱相伴随，而在老年动物中，通过核因子κB受体活化剂（RANKL）表达的增加，配体骨丢失和破骨细胞生成增多相伴随。PPARγ活性的增加导致骨髓结构和功能的改变，比如成骨细胞的减少，骨髓脂肪细胞的增加，破骨细胞的增加，以及骨髓间质干细胞多能分化特性的减退。总之，罗格列酮导致的骨改变和骨老化类似，并可能通过改变骨髓间质干细胞的表型导致了骨丢失。
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作者:admin@医学,生命科学 2011-02-13 05:12
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