Effects of Systemic Peroxisome Proliferator-Activated Receptor Gamma Inhibition on Bone and Immune Cells in Aged
Xingming Shi1, Kehong Ding1, Raysa Rosario1
1Department of Neuroscience and Regenerative Medicine, Augusta University, Augusta, Georgia, USA.
Abstract:
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.
Insights
PPARγ inhibition negatively impacts bone structure in aged female mice, despite increasing osteogenic gene expression and reducing inflammation markers in vitro. Immune cell composition remained unaffected.
Area of Science:
- Bone Biology
- Immunology
- Cellular Biology
Background:
- Peroxisome proliferator-activated receptor gamma (PPARγ) plays a role in bone metabolism and immune function.
- Aging is associated with bone loss and altered immune responses.
Purpose of the Study:
- To investigate the effects of PPARγ inhibition on bone mass, immune cell profiles, and in vitro osteogenic/adipogenic differentiation in aged female mice.
- To assess the impact of PPARγ inhibition on inflammation-related gene expression.
Main Methods:
- Aged female mice were treated with a PPARγ antagonist (GW9662) for 6 weeks.
- Bone microarchitecture was analyzed using micro-computed tomography.
- Immune cell composition in marrow and spleen was assessed.
- In vitro studies examined stromal stem cell osteogenic and adipogenic differentiation and gene expression.
Main Results:
- PPARγ inhibition led to reduced bone volume, trabecular number, and increased trabecular spacing in aged female mice.
- No significant changes were observed in marrow and spleen immune cell composition.
- In vitro, GW9662 treatment enhanced osteogenic gene expression but did not affect adipogenic genes.
- GW9662 treatment decreased the expression of several inflammation-related genes.
Conclusions:
- PPARγ inhibition may have detrimental effects on bone structure in aged female mice.
- While PPARγ inhibition shows potential for reducing inflammation and promoting osteogenesis in vitro, its in vivo effects on bone are negative.
- Further research is needed to elucidate the complex role of PPARγ in aging bone and immunity.
More Related Videos
06:18An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
06:49Orthotopic Ovarian Transplantation Procedures to Investigate the Life- and Health-span Influence of Ovarian Senescence in Female Mice
Published on: February 12, 2018
