Defects in a liver-bone axis contribute to hepatic osteodystrophy disease progression

Hepatic osteodystrophy (HOD) is a metabolic bone disease that is often associated with chronic liver disease and is marked by bone loss. Here, we demonstrate that hepatic expression of the phosphatase PP2Aca is upregulated during HOD, leading to the downregulation of expression of the hepatokine lecithin-cholesterol acyltransferase (LCAT). Loss of LCAT function markedly exacerbates the bone loss phenotype of HOD in mice. In addition, we found that alterations in cholesterol levels are involved in the regulation of osteoblast and osteoclast activities. We also found that LCAT improves liver function and relieves liver fibrosis in the mouse HOD model by promoting reversal of cholesterol transport from the bone to the liver. In summary, defects in a liver-bone axis occur during HOD that can be targeted to ameliorate disease progression.

Automated summary

Hepatic osteodystrophy (HOD) is a metabolic bone disease associated with chronic liver disease. Upregulation of the phosphatase PP2Aca in the liver during HOD leads to downregulation of hepatokine lecithin-cholesterol acyltransferase (LCAT). Loss of LCAT function exacerbates bone loss in HOD mice. Cholesterol levels play a role in the regulation of osteoblast and osteoclast activities. LCAT improves liver function and reduces liver fibrosis in the HOD mouse model by promoting cholesterol transport from bone to liver.