Objective To Investigate the effects of lithocholic acid (LCA) on the balance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Methods Twelve 10-week-old SPF C57BL/6J female mice were randomly divided into an experimental group (undergoing bilateral ovariectomy) and a control group (only removing the same volume of adipose tissue around the ovaries), with 6 mice in each group. The body mass was measured every week after operation. After 4 weeks post-surgery, the weight of mouse uterus was measured, femur specimens of the mice were taken for micro-CT scanning and three-dimensional reconstruction to analyze changes in bone mass. Tibia specimens were taken for HE staining to calculate the number and area of bone marrow adipocytes in the marrow cavity area. ELISA was used to detect the expression of bone turnover markers in the serum. Liver samples were subjected to real-time fluorescence quantitative PCR (RT-qPCR) to detect the expression of key genes related to bile acid metabolism, including cyp7a1, cyp7b1, cyp8b1, and cyp27a1. BMSCs were isolated by centrifugation from 2 C57BL/6J female mice (10-week-old). The third-generation cells were exposed to 0, 1, 10, and 100 μmol/L LCA, following which cell viability was evaluated using the cell counting kit 8 assay. Subsequently, alkaline phosphatase (ALP) staining and oil red O staining were conducted after 7 days of osteogenic and adipogenic induction. RT-qPCR was employed to analyze the expressions of osteogenic-related genes, namely ALP, Runt-related transcription factor 2 (Runx2), and osteocalcin (OCN), as well as adipogenic-related genes including Adiponectin (Adipoq), fatty acid binding protein 4 (FABP4), and peroxisome proliferator-activated receptor γ (PPARγ). Results Compared with the control group, the body mass of the mice in the experimental group increased, the uterus atrophied, the bone mass decreased, the bone marrow fat expanded, and the bone metabolism showed a high bone turnover state. RT-qPCR showed that the expressions of cyp7a1, cyp8b1, and cyp27a1, which were related to the key enzymes of bile acid metabolism in the liver, decreased significantly (P<0.05), while the expression of cyp7b1 had no significant difference (P>0.05). Intervention with LCA at concentrations of 1, 10, and 100 μmol/L did not demonstrate any apparent toxic effects on BMSCs. Furthermore, LCA inhibited the expressions of osteogenic-related genes (ALP, Runx2, and OCN) in a dose-dependent manner, resulting in a reduction in ALP staining positive area. Concurrently, LCA promoted the expressions of adipogenic-related genes (Adipoq, FABP4, and PPARγ), and an increase in oil red O staining positive area. Conclusion After menopause, the metabolism of bile acids is altered, and secondary bile acid LCA interferes with the balance of osteogenic and adipogenic differentiation of BMSCs, thereby affecting bone remodelling.
ObjectiveTo systematically review the correlation between the triglyceride-glucose index (TyG index) and pulse wave velocity (PWV) and explore the relationship between the TyG index and arterial stiffness (AS). MethodsThe PubMed, Embase, Web of Science, CBM, WanFang Data, and CNKI databases were searched to collect observational studies on the correlation between the TyG index and AS from inception to January 14, 2024. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. Meta-analysis was performed using RevMan 5.4 software. ResultsA total of 16 studies were included. The results of the meta-analysis showed that when the TyG index was used as a continuous variable to evaluate its correlation with AS based on brachial-ankle pulse wave velocity (baPWV) as the outcome parameter, individuals with high TyG index had higher baPWV compared to those with low TyG index (OR=1.48, 95%CI 1.27 to 1.72, P<0.001). Similar correlations were observed when the TyG index was used as a categorical variable to evaluate its correlation with AS (OR=1.85, 95%CI 1.67 to 2.04, P<0.001). When carotid-femoral pulse wave velocity (cfPWV) was used as the outcome parameter, individuals with high TyG index had higher cfPWV compared to those with low TyG index when the TyG index was used as a continuous variable (OR=1.47, 95%CI 1.11 to 1.95, P=0.008). Similar correlations were observed when the TyG index was used as a categorical variable to evaluate its correlation with AS (OR=1.34, 95%CI 1.21 to 1.48, P<0.001). Subgroup analysis results showed that when the TyG index was used as a continuous variable, the correlation between the TyG index and baPWV was independent of gender, age, participant characteristics, and study type. When the TyG index was used as a categorical variable, the correlation between the TyG index and baPWV was independent of age and participant characteristics. Using high baPWV to define AS, when the TyG index was used as a continuous variable to evaluate its impact on AS, individuals with high TyG index had a higher likelihood of AS compared to those with low TyG index (OR=1.51, 95%CI 1.36 to 1.67, P<0.001). Similar correlations were observed when the TyG index was used as a categorical variable to evaluate its correlation with AS (OR=1.81, 95%CI 1.48 to 2.21, P<0.001). Using high cfPWV to define AS, when the TyG index was used as a continuous variable to evaluate its impact on arterial stiffness, individuals with a high TyG index had a higher likelihood of AS compared to those with a low TyG index (OR=1.30, 95%CI 1.10 to 1.53, P=0.02). Similar correlations were observed when the TyG index was used as a categorical variable to evaluate its correlation with AS (OR=1.60, 95%CI 1.33 to 1.92, P<0.001). Subgroup analysis results showed that when the TyG index was used as a continuous variable, the correlation between the TyG index and AS was independent of gender, participant characteristics, age, hypertension, and diabetes. When the TyG index was used as a categorical variable, the correlation between the TyG index and AS was independent of gender, participant characteristics, age, and hypertension. ConclusionThere is a strong correlation between the TyG index and PWV, with a higher TyG index associated with increased PWV and greater risk of AS. The TyG index can serve as a simple alternative marker for early diagnosis of AS and guide clinical intervention. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.