Role of fatty acid-protein 4 (FABP4) in the pathogenesis of post-menopause osteoporosis

Abstract

As osteoporosis (OP) and obesity are major public chronic diseases, scientists carried on long-term research on the relationship between osteoporosis and obesity. Previous studies revealed that obesity is a protective factor for osteoporosis, whereas, recently some studies mentioned that obesity can accelerate osteoporosis. In our studies, the result of Micro CT in pre-experiment revealed that the parameters of bone mineral density and bone trabecular structure in the mice fed with high fat diet (HFD)without OVX surgery is really better than that in STD mice, but there is no significant influence between two groups (P > 0.05). Whereas, after the OVX operation, HFD fed mice has an obvious decreasing in the bone mineral density and trabecular structure parameters than those with STD mice (P < 0.05 or P < 0.01). These results indicate that there is a closely relationship between obesity and osteoporosis correlation with body's physiological cycle, especially the deficiency of estrogen level in post-menopausal will promote the adipogenesis and inhibit the formation of osteoblasts, which lead to induce osteoporosis. To date existing publications, osteoblasts and adipocytes originate from the common ancestral cell, the bone marrow mesenchymal stem cells (BMMSC), however they restrain each other, which means stimulating MSC differentiate to adipocytes can inhibit the formation of osteoblasts, which lead to post-osteoporosis. It is worth mentioning that peroxisome proliferator-activated receptor γ (PPARγ) is the major pathway of adipogenesis differentiation, and among them FABP4 as a downstream target of PPAR γ play a vital role in the signal pathway. Meanwhile, we also observed that body fat cells showed a significant increase in clinical postmenopausal women. Therefore, we concluded that FABP4 plays an important role in physiologic bone regulation through PPARγ signaling, but it is still not clear whether the pathway is reverse in order to protect people from suffering osteoporosis. Hence, we hypothesis that inhibiting the expression of the FABP 4 can block adipogenesis, increase the expression of osteogenic, which can protect HFD-induced mice from post-menopaused osteoporosis. We adopt FABP4 gene knockout mice with OVX operation as model to verify our hypothesis. According to our research result, the FABP(-/-) mice can decrease the incidence of post-menopause from 95% to 86%. Western blotting also prove that there is no expression in peripheral tissue in FABP(/-) mice (Figure 18) , all the results support our hypothesis. Together with, in the process of regulation of differentiation of BMMSCs, FABP4 is key regulatory targets in the pathway of PPARγ, inhibiting FABP4 expression can be reversed in the morbidity of postmenopausal osteoporosis. Therefore, further research plays a crucial role on the early clinical diagnosis, early prevention and targeted therapy of postmenopausal osteoporosis.