Bilirubin and bile acids in osteocytes and bone tissue. Potential role in the cholestatic‐induced osteoporosis

Ruiz-Gaspà, Sílvia; Guañabens, Núria; Jurado, Susana Beatriz; Combalía, A.; Peris, Pilar; Monegal, Ana; Parés, Albert

doi:10.1111/liv.14630

Cited by 17 publications

(11 citation statements)

References 37 publications

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“…Interestingly, in the present study, LCA was significantly increased in the DIO group compared to the CON group. Previous studies have further demonstrated the deleterious consequences of LCA and bilirubin on osteoblastic cells (Ruiz-Gaspà et al, 2020a;Ruiz-Gaspà et al, 2020b). Low bone formation due to diminished osteoblast activity is the main cause of bone loss (Guañabens et al, 1990).…”

Section: Discussionmentioning

confidence: 98%

Gut microbiota and fecal metabolic signatures in rat models of disuse-induced osteoporosis

Qiao

Zhang²,

Li³

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundAssessing the correlation between gut microbiota (GM) and bone homeostasis has increasingly attracted research interest. Meanwhile, GM dysbiosis has been found to be associated with abnormal bone metabolism. However, the function of GM in disuse-induced osteoporosis (DIO) remains poorly understood. In our research, we evaluated the characteristics of GM and fecal metabolomics to explore their potential correlations with DIO pathogenesis.MethodsDIO rat models and controls (CON) underwent micro-CT, histological analyses, and three-point bending tests; subsequently, bone microstructures and strength were observed. ELISAs were applied for the measurement of the biochemical markers of bone turnover while GM abundance was observed using 16S rDNA sequencing. Metabolomic analyses were used to analyze alterations fecal metabolites. The potential correlations between GM, metabolites, and bone loss were then assessed.ResultsIn the DIO group, the abundance of GM was significantly altered compared to that in the CON group. Moreover, DIO significantly altered fecal metabolites. More specifically, an abnormally active pathway associated with bile acid metabolism, as well as differential bacterial genera related to bone/tissue volume (BV/TV), were identified. Lithocholic acid, which is the main secondary bile acid produced by intestinal bacteria, was then found to have a relationship with multiple differential bacterial genera. Alterations in the intestinal flora and metabolites in feces, therefore, may be responsible for DIO-induced bone loss.ConclusionsThe results indicated that changes in the abundance of GM abundance and fecal metabolites were correlated with DIO-induced bone loss, which might provide new insights into the DIO pathogenesis. The detailed regulatory role of GM and metabolites in DIO-induced bone loss needs to be explored further.

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Section: Discussionmentioning

confidence: 98%

Gut microbiota and fecal metabolic signatures in rat models of disuse-induced osteoporosis

Qiao

Zhang²,

Li³

et al. 2022

Front. Cell. Infect. Microbiol.

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“…One obvious question based on our findings was if the increased levels of circulating bile acids would affect bone remodeling and potentially cause the decreased trabecular bone mass in PSC OPO patients. Indeed, there are previous studies suggesting that bile acids may influence the activity of bone remodeling cell types 19 , 20 , and an influence of the farnesoid X receptor (FXR), which functions as an intracellular bile acid sensor, on bone formation and resorption has been described 21 , 22 . Importantly, however, it has not been addressed yet, if the conjugated forms of bile acids would cause similar influences, which is a key question, since they are known to act through different receptor signaling complexes when compared to the unconjugated forms 23 .…”

Section: Discussionmentioning

confidence: 99%

Increased concentrations of conjugated bile acids are associated with osteoporosis in PSC patients

Stürznickel

Behler-Janbeck

Baranowsky

et al. 2022

Sci Rep

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Primary sclerosing cholangitis (PSC) is an idiopathic cholestatic liver disease characterized by chronic inflammation and progressive fibrosis of intra- and extrahepatic bile ducts. Osteoporosis is a frequent comorbidity in PSC, and we could previously demonstrate that IL17-dependent activation of bone resorption is the predominant driver of bone loss in PSC. Since we additionally observed an unexpected heterogeneity of bone mineral density in our cohort of 238 PSC patients, the present study focused on a comparative analysis of affected individuals with diagnosed osteoporosis (PSCOPO, n = 10) or high bone mass (PSCHBM, n = 7). The two groups were not distinguishable by various baseline characteristics, including liver fibrosis or serum parameters for hepatic function. In contrast, quantification of serum bile acid concentrations identified significant increases in the PSCOPO group, including glycoursodeoxycholic acid (GUDCA), an exogenous bile acid administered to both patient groups. Although cell culture experiments did not support the hypothesis that an increase in circulating bile levels is a primary cause of PSC-associated osteoporosis, the remarkable differences of endogenous bile acids and GUDCA in the serum of PSCOPO patients strongly suggest a yet unknown impairment of biliary metabolism and/or hepatic bile acid clearance in this patient subgroup, which is independent of liver fibrosis.

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“… 162 Furthermore, LCA and bilirubin were proven to have detrimental effects on the activity, differentiation and mineralization of osteoblasts, but these impacts could be neutralized by UDCA, suggesting that UDCA could be recognized as a potential therapeutic agent in osteoporotic patients with primary biliary cholangitis. 163 , 164 TUDCA, an FDA-approved hydrophilic BA for the treatment of chronic cholestatic liver disease, was proven to be a potent drug for ovariectomized mice at different concentrations. By administering TUDCA, more small beam structures in the distal femur were preserved, and other indices, such as total bone volume, bone mineral density, and bone volume percentage, were significantly improved compared to the control group.…”

Section: Bile Acid Network and Vascular Calcification-associated Dise...mentioning

confidence: 99%

Bile Acid Network and Vascular Calcification-Associated Diseases: Unraveling the Intricate Connections and Therapeutic Potential

Wang,

Ma,

2023

CIA

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Bile acids play a crucial role in promoting intestinal nutrient absorption and biliary cholesterol excretion, thereby protecting the liver from cholesterol accumulation and bile acid toxicity. Additionally, bile acids can bind to specific nuclear and membrane receptors to regulate energy expenditure and specific functions of particular tissues. Vascular calcification refers to the pathological process of calcium-phosphate deposition in blood vessel walls, which serves as an independent predictor for cardiovascular adverse events. In addition to aging, this pathological change is associated with aging-related diseases such as atherosclerosis, hypertension, chronic kidney disease, diabetes mellitus, and osteoporosis. Emerging evidence suggests a close association between the bile acid network and these aforementioned vascular calcification-associated conditions. Several bile acids have been proven to participate in calcium-phosphate metabolism, affecting the transdifferentiation of vascular smooth muscle cells and thus influencing vascular calcification. Targeting the bile acid network shows potential for ameliorating these diseases and their concomitant vascular calcification by regulating pathways such as energy metabolism, inflammatory response, oxidative stress, and cell differentiation. Here, we present a summary of the metabolism and functions of the bile acid network and aim to provide insights into the current research on the profound connections between the bile acid network and these vascular calcification-associated diseases, as well as the therapeutic potential.

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Bilirubin and bile acids in osteocytes and bone tissue. Potential role in the cholestatic‐induced osteoporosis

Cited by 17 publications

References 37 publications

Gut microbiota and fecal metabolic signatures in rat models of disuse-induced osteoporosis

Gut microbiota and fecal metabolic signatures in rat models of disuse-induced osteoporosis

Increased concentrations of conjugated bile acids are associated with osteoporosis in PSC patients

Bile Acid Network and Vascular Calcification-Associated Diseases: Unraveling the Intricate Connections and Therapeutic Potential

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