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Updated: May 9, 2025

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
Published on: March 15, 2018
The p53-miR17 family-Rankl axis bridges liver-bone communication
Guixing Ma1, Siyuan Cheng1, Yingying Han1
1Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen 518055, China.
Abstract:
Our study elucidates the crucial role of the liver in bone homeostasis through the p53-miR17 family (miR17-miR20/miR20-miR106/miR93-miR106)-Rankl axis. We demonstrate the enhanced hepatocyte Rankl expression in inflammaging conditions, such as aging, ovariectomized (OVX) mice, and elderly humans. Mice with hepatocyte-specific Rankl deletion exhibit significant resistance to bone mass loss associated with aging, lipopolysaccharide (LPS)-induced inflammation, or estrogen deficiency, compared with controls. Our study highlights hepatocytes as the primary source of Rankl in the liver and serum under these conditions. We identify the p53-miR17 family axis as a crucial regulator for hepatocyte Rankl expression, with p53 inhibiting the miR17 family transcription. Through bioinformatics analysis and in vitro validation, we identify Rankl mRNA as a direct target of the miR17 family. Targeting this axis via CasRx-mediated mRNA editing or miRNA interference significantly attenuates bone mass loss in mice. Our investigation underscores the pivotal significance and therapeutic potential of modulating the p53-miR17 family-Rankl axis in the treatment of inflammaging-associated osteoporosis.
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