Health

Chronic liver damage causes bone loss


This mutual regulation of liver and bone is called the liver-bone axis. External stimuli, such as viruses, alcohol and drugs, can cause chronic liver damage, which then affects bone metabolism across the liver-bone axis, leading to an increased risk of osteoporosis and fractures easy to break.

Fractures caused by HOD disease make bone remodeling difficult, and seriously affect the prognosis and quality of life of HOD patients. Therefore, it is important to elucidate the mechanisms of HOD.

In HOD patients and HOD mouse models, the team found high expression of PP2Acα. “Conditional knockout of PP2Acα in the liver of HOD mice restores liver function and alleviates bone loss” GS Chen said.

Through proteomics analysis, the research team screened and identified the liver factor LCAT, which regulates the liver-skeletal axis. As a cholesterol-transfer enzyme, LCAT can transfer cholesterol from peripheral tissues to the liver, a process known as cholesterol reverse transport (RCT).

“LCAT mediates bone metabolism by maintaining appropriate intracellular cholesterol levels and improves liver function by reversing cholesterol transport from bone tissue to the liver”.

RCTs play an important role in the maintenance of liver-skeletal homeostasis. Appropriate levels of intracellular cholesterol can promote osteoblast function and inhibit osteoclast differentiation.

In HOD patients and mouse models of HOD, the researchers found that PP2Acα downregulates LCAT expression in HOD.

This study indicates that an imbalance of the hepatoskeletal axis accelerates the progression of HOD due to chronic liver injury. It also provides a potential target for the development of therapeutic drugs for the treatment of liver disease.

Source: Eurekalert



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