Artikel
Inflammatory response in osteoporotic senile rat model: impact of estrogen and dietary deficiencies
Suche in Medline nach
Autoren
Veröffentlicht: | 22. Oktober 2019 |
---|
Gliederung
Text
Objectives: Estrogen plays an important role in bone homeostasis and skeletal growth. Estrogen deficiency is correlated to discrepant inflammatory response and deteriorated bone matrix quality among post-menopausal osteoporotic patients. Commonly, osteoporosis induction combines ovariectomy with dietary deficiency. This study examines the effect of estrogen deficiency and dietary deficiency combined and separately deficiency on osteo-immunology in a rat model of senile osteoporosis to predict regulatory interaction between bone and inflammatory cells.
Methods: 46 female Sprague-Dawley rats (age=12 months) were divided into five groups: 1) Control group (M = Months) (0M), 2) Sham operated (Sham, 3M), 3) bilaterally ovariectomized (OVX, 3M), 4) Sham operated combined with diet-deficiency (Diet, 3M), and 5) OVX combined with diet-deficiency (OVXD, 3M). After euthanasia using cardiac puncture, serum analysis as well as molecular analysis of the spine were performed. Histological analysis was carried out on the long bone samples. The underlying interactions among bone markers and inflammatory markers were predicted using bioinformatics approach.
Results and conclusion: Histomorphometry of Von Kossa/Van Gieson staining showed significantly lower mineralized and non-mineralized matrix in OVX, Diet, and OVXD when compared with Sham (p-value ≤ 0.05, both). The number of monocytes within the bone marrow of OVX and OVXD was higher compared with other groups. Serum analysis revealed higher level of interleukins (IL-1, IL-10, and IL-13) as well as bone markers like leptin, SPP1, OPG, TNF- α showed higher level in OVX when compared with other groups. Furthermore, molecular analysis showed upregulation of Il-13 and downregulation of Il-4 in both OVX and OVXD compared with control. Il-13 was downregulated in Sham and Diet compared with Control. Il-4 was upregulated in Sham and downregulated in Diet compared with Control. Spp1 and Opg showed lower relative gene expression in OVX compared with Sham. Network analysis resulted in co-expression between the immune cells and the bone cells.
Inflammatory response was reported to coordinate recruitment of mesenchymal stem cells, neo-angiogenesis, endochondral ossification and bone remodeling in estrogen deficient osteoporotic rats. However, most information were reported in a fracture setup. Here we show dysregulation in major cytokines involved in shifting macrophage phenotypes from pro-inflammatory M1 to anti-inflammatory M2 (IL-1 and IL-10) caused by dietary deficiency as well as estrogen deficiency. Interestingly, combination of treatment did not increase the effect on these cytokines significantly. Currently we are addressing the expression of IL-6 as other major cytokine affected by estrogen. Immunostainings of innate (M1 and M2 macrophage) and adaptive immune cells (B and T cells) are being carried out to unravel cellular alterations under dietary or estrogen deficiencies.