Clinical Research Center, University College Dublin, Belfield, 4 Dublin, Ireland.
PPAR Res. 2009;2009:421376. doi: 10.1155/2009/421376. Epub 2009 Mar 23.
Currently infection with the human immunodeficiency virus-1 (HIV-1) is in most instances a chronic disease that can be controlled by effective antiretroviral therapy (ART). However, chronic use of ART has been associated with a number of toxicities; including significant reductions in bone mineral density (BMD) and disorders of the fat metabolism. The peroxisome proliferator-activated receptor γ (PPARγ) transcription factor is vital for the development and maintenance of mature and developing adipocytes. Alterations in PPARγ expression have been implicated as a factor in the mechanism of HIV-1-associated lipodystrophy. Both reduced BMD and lipodystrophy have been well described as complications of HIV-1 infection and treatment, and a question remains as to their interdependence. Interestingly, both adipocytes and osteoblasts are derived from a common precursor cell type; the mesenchymal stem cell. The possibility that dysregulation of PPARγ (and the subsequent effect on both osteoblastogenesis and adipogenesis) is a contributory factor in the lipid- and bone-abnormalities observed in HIV-1 infection and treatment has also been investigated. This review deals with the hypothesis that dysregulation of PPARγ may underpin the bone abnormalities associated with HIV-1 infection, and treats the current knowledge and prospective developments, in our understanding of PPARγ involvement in HIV-1-associated bone disease.
目前，人体免疫缺陷病毒 1（HIV-1）的感染在大多数情况下是一种慢性疾病，可以通过有效的抗逆转录病毒疗法（ART）来控制。然而，慢性使用 ART 与许多毒性有关；包括骨密度（BMD）显著降低和脂肪代谢紊乱。过氧化物酶体增殖物激活受体 γ（PPARγ）转录因子对于成熟和发育中的脂肪细胞的发育和维持至关重要。PPARγ 表达的改变被认为是 HIV-1 相关脂肪营养不良机制中的一个因素。骨密度降低和脂肪营养不良都被很好地描述为 HIV-1 感染和治疗的并发症，它们之间的相互依存关系仍存在疑问。有趣的是，脂肪细胞和成骨细胞都来源于一种共同的前体细胞类型；间充质干细胞。PPARγ 失调（以及对成骨细胞生成和脂肪生成的后续影响）是否是 HIV-1 感染和治疗中观察到的脂质和骨骼异常的一个促成因素，这一可能性也得到了研究。这篇综述探讨了这样一种假设，即 PPARγ 的失调可能是与 HIV-1 感染相关的骨骼异常的基础，并探讨了我们对 PPARγ 参与 HIV-1 相关骨骼疾病的理解的当前知识和未来发展。
