| Abstract |
Metabolic dysfunction-associated steatohepatitis (MASH) is a liver disease characterized by hepatic steatosis and inflammation that can progress to severe conditions. MASH affects systemic organs, leading to hepatic osteodystrophy with bone weakness and an increased risk of fractures. Although calcium supplementation is commonly used to alleviate hepatic osteodystrophy, it often has no effect. Therefore, we focused on fibroblast growth factor 23 (FGF23) as a potential causative factor for hepatic osteodystrophy, given its critical role in regulating phosphorus, another key component of bone. MASH mouse models were generated using a choline- and methionine-deficient high-fat diet. Histological and biochemical analyses confirmed severe hepatic steatosis and inflammation in the MASH mice. Micro-computed tomography analysis revealed decreased bone mineral density and trabecular number, with increased trabecular separation, indicating weakened bones in MASH mice. Although serum FGF23 levels were elevated in MASH mice, serum phosphorus levels remained unchanged. This led us to examine the effects of FGF23 on bone remodeling by osteoblasts and osteoclasts, and we found that FGF23 promoted osteoclast differentiation and suppressed osteoblast differentiation. Our findings suggest that MASH-induced elevation of FGF23 contributes to an imbalance in bone remodeling, leading to hepatic osteodystrophy.
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