biostudies-literatureChen YGuangdong Science and Technology Department (Science and Technology Department, Guangdong Province)National Natural Science Foundation of China (National Science Foundation of China)803https://www.ebi.ac.uk/biostudies/studies/S-EPMC9489716biostudies-literatureUnknown13(9)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, leadingCell death & diseaseHnrnpk maintains chondrocytes survival and function during growth plate development via regulating Hif1α-glycolysis axis.PMC948971682172376920681052020A151511002582072385Liao ZLiu HYang XWu JSu DLi YSu PZhou TXu CChen YGao WZhang SfalseHnrnpk 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 Hif1α, leading2022-01-01T00:00:00Z2022 Sep2025-04-22T10:56:02.942Z2025-04-05T23:49:30.454ZS-EPMC94897163612732510.1038/s41419-022-05239-0