ABSTRACT
BACKGROUNDS: Nonalcoholic fatty liver disease (NAFLD) exhibits a close association with osteoporosis. This work aims to assess the potential effects of NAFLD on the progression of osteopenia in animal models. METHODS: Forty-eight C57BL/6 female mice were randomly divided to wild-type (WT) group and high-fat diet (HFD) group. The corresponding detections were performed after sacrifice at 16, 24 and 32 weeks, respectively. RESULTS: At 16 weeks, an remarkable increase in body weight and lipid aggregation in the hepatocytes of HFD group was observed compared to the WT group, while the bone structure parameters showed no significant difference. At 24 weeks, the levels of TNF-α and IL-6 in NAFLD mice were significantly increased, while the level of osteoprotegerin mRNA in bone tissue was decreased, and the level of receptor activator of nuclear factor Kappa-B ligand mRNA was increased. Meanwhile, the function of osteoclasts was increased, and the bone microstructure parameters showed significant changes. At 32 weeks, in the HFD mice, the mRNA levels of insulin-like growth factor-1 (IGF-1), runt-related transcription factor 2, and osterix mRNA were reduced, while the insulin-like growth factor binding protein-1 (IGFBP-1) level was increased. Simultaneously, the osteoblast function was decreased, and the differences of bone structure parameters were more significant, showing obvious osteoporosis. CONCLUSIONS: The bone loss in HFD mice is pronounced as NAFLD progresses, and the changes of the TNF-α, IL-6, IGF-1, and IGFBP-1 levels may play critical roles at the different stages of NAFLD in HFD.
Subject(s)
Non-alcoholic Fatty Liver Disease , Osteoporosis , Female , Mice , Animals , Non-alcoholic Fatty Liver Disease/complications , Tumor Necrosis Factor-alpha/metabolism , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor Binding Protein 1/genetics , Interleukin-6/metabolism , Mice, Inbred C57BL , Osteoporosis/complications , RNA, Messenger/metabolismABSTRACT
OBJECTIVE: To explore the expression pattern of amyloid beta-protein (Aß) in bone tissue and elucidate its possible effects on bone metabolism of proximal tibia in APP/PS1 transgenic mouse. METHODS: Immunohistochemistry and immunofluorescence were used to analyze the horizontal and longitudinal sections of proximal tibia in 9-month-old APP/PS1 transgenic mouse. And the tissues of APP/PS1 transgenic and wild-type mice were harvested to analyze the serum levels of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA). Micro-computed tomography (micro-CT) was used to analyze the changes of bone microarchitecture and bone mineral density (BMD) of proximal tibia. RESULTS: Aß was expressed in bone trabecular and osteocytes of proximal tibia in APP/PS1 transgenic mouse. As compared with wild-type mice (32.1 ± 6.8; 28.9 ± 4.5; 3.17 ± 0.26; 3.17 ± 0.26; 1229 ± 113), the serum levels of TNF-α (42.3 ± 7.4) and IL-6 (40.9 ± 6.7) of APP/PS1 transgenic mice significantly increased. However bone microarchitecture (1.95 ± 0.22) and BMD (187 ± 29; 1109 ± 104) of proximal tibia were significantly lower on micro-CT (P < 0.05). CONCLUSION: Aß is expressed in bone tissue and it is associated with the changes of bone mineral density. Thus it may play an important role in the pathogenesis of osteoporosis through the changes of TNF-α and IL-6 in APP/PS1 transgenic mouse.
Subject(s)
Amyloid beta-Peptides/metabolism , Bone and Bones/metabolism , Presenilin-1/genetics , Animals , Bone Density , Female , Interleukin-6/blood , Mice , Mice, Inbred C57BL , Mice, Transgenic , Osteocytes/metabolism , Tumor Necrosis Factor-alpha/bloodABSTRACT
Alzheimer's disease and osteoporosis are often observed to co-occur in clinical practice. The present study aimed to evaluate the bone microarchitecture and bone mineral density (BMD) of the proximal tibia in APP/PS1 transgenic mice by micro-computed tomography (micro-CT), and to search for evidence that curcumin can be used to reduce bone mineral losses and treat osteoporosis after senile dementia in these transgenic mice. Three-month-old female mice were divided into the following groups (n=9 per group): wild-type mice (WT group); APP/PS1 transgenic mice (APP group); and APP/PS1 transgenic mice with curcumin treatment (APP+Cur group). Between 9 and 12 months of age, the APP+Cur group were administered curcumin orally (600ppm). CT scans of the proximal tibia were taken at 6, 9 and 12 months. At 6 months, there were little differences in the structural parameters. At 9 months, the APP groups displayed loss of bone volume ratio (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and connectivity density (Conn.D) and increases in trabecular separation (Tb.Sp) and geometric degree of anisotropy (DA) (P<0.05 or P<0.01), with significant changes in the BMD parameters. At 12 months, curcumin treatment led to constant increases in the trabecular bone mass of the metaphysis and clearly improved the BMD. By the same time, we measured the TNF-α and IL-6 in the serum among the different groups at 6, 9 and 12 months by enzyme-linked immunoassay(ELISA). These results suggest that APP/PS1 transgenic mice are susceptible to osteoporosis, and that curcumin can prevent further deterioration of the bone structure and produce beneficial changes in bone turnover. The change of inflammation cytokine, including TNF-α and IL-6, may play an important role in the mechanisms of action of curcumin, but the detail mechanism remains unknown.