Hnrnpk maintains chondrocytes survival and function during growth plate development via regulating Hif1α-glycolysis axis

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 Hif1 alpha, 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 Hif1 alpha-glycolysis axis through a post-transcriptional mechanism during growth plate development.

Automated summary

This study reveals the essential role of Hnrnpk in maintaining the appropriate intensity of glycolysis in chondrocytes and orchestrating growth plate development. Hnrnpk deficiency leads to dwarfism and increased bone mass by enhancing the transdifferentiation of chondrocytes and promoting excessive glycolysis. The mechanism involves Hnrnpk binding to Hif1a mRNA and promoting its degradation, which results in increased expression of downstream glycolytic enzymes.