Department of Neuroscience and Regenerative Medicine, Augusta University, Augusta, Georgia, USA.
Center for Molecular Chaperone/Radiobiology and Cancer Virology, Augusta University, Augusta, Georgia, USA.
J Gerontol A Biol Sci Med Sci. 2024 Feb 1;79(2). doi: 10.1093/gerona/glad247.
This study investigates the effects of peroxisome proliferator-activated receptor gamma (PPARγ) inhibition on bone and immune cell profiles in aged female mice, as well as in vitro stromal stem cell osteogenic differentiation and inflammation gene expression. The hypothesis was that inhibition of PPARγ would increase bone mass and alter immune and other cellular functions. Our results showed that treatment with PPARγ antagonist GW9662 for 6 weeks reduced bone volume and trabecular number and increased trabecular spacing. However, inhibition of PPARγ had no significant effect on marrow and spleen immune cell composition in aged female mice. In vitro experiments indicated that GW9662 treatment increased the expression of osteogenic genes but did not affect adipogenic genes. Additionally, GW9662 treatment decreased the expression of several inflammation-related genes. Overall, these findings suggest that PPARγ inhibition may have adverse effects on bone in aged female mice.
本研究旨在探讨过氧化物酶体增殖物激活受体 γ（PPARγ）抑制对老年雌性小鼠骨和免疫细胞特征的影响，以及体外基质干细胞成骨分化和炎症基因表达的影响。假设是抑制 PPARγ 会增加骨量并改变免疫和其他细胞功能。我们的研究结果表明，用 PPARγ 拮抗剂 GW9662 治疗 6 周会减少骨体积和小梁数量，增加小梁间距。然而，抑制 PPARγ 对老年雌性小鼠骨髓和脾脏免疫细胞组成没有显著影响。体外实验表明，GW9662 处理增加了成骨基因的表达，但不影响成脂基因的表达。此外，GW9662 处理还降低了几个与炎症相关的基因的表达。总的来说，这些发现表明，PPARγ 抑制可能对老年雌性小鼠的骨骼产生不良影响。
