Hnrnpk Maintains Chondrocytes Survival and Function During Growth Plate Development Via Regulating Hif1α-glycolysis Axis

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2022 Sep 20

PMID 36127325

Authors

Yuyu Chen

Jinna Wu

Shun Zhang

Wenjie Gao

Zhiheng Liao

Taifeng Zhou

Yongyong Li

Deying Su

Hengyu Liu

Xiaoming Yang

Peiqiang Su

Caixia Xu

Affiliations

Soon will be listed here.

Abstract

The harmonious functioning of growth plate chondrocytes is crucial for skeletogenesis. These cells rely on an appropriate intensity of glycolysis to maintain survival and function in an avascular environment, but the underlying mechanism is poorly understood. Here we show that Hnrnpk orchestrates growth plate development by maintaining the appropriate intensity of glycolysis in chondrocytes. Ablating Hnrnpk causes the occurrence of dwarfism, exhibiting damaged survival and premature differentiation of growth plate chondrocytes. Furthermore, Hnrnpk deficiency results in enhanced transdifferentiation of hypertrophic chondrocytes and increased bone mass. In terms of mechanism, Hnrnpk binds to Hif1a mRNA and promotes its degradation. Deleting Hnrnpk upregulates the expression of Hif1α, leading to the increased expression of downstream glycolytic enzymes and then exorbitant glycolysis. Our study establishes an essential role of Hnrnpk in orchestrating the survival and differentiation of chondrocytes, regulating the Hif1α-glycolysis axis through a post-transcriptional mechanism during growth plate development.

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