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 gr...

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Published inCell death & disease Vol. 13; no. 9; p. 803
Main Authors Chen, Yuyu, Wu, Jinna, Zhang, Shun, Gao, Wenjie, Liao, Zhiheng, Zhou, Taifeng, Li, Yongyong, Su, Deying, Liu, Hengyu, Yang, Xiaoming, Su, Peiqiang, Xu, Caixia
Format Journal Article
LanguageEnglish
Published England Springer Nature B.V 20.09.2022
Nature Publishing Group UK
Nature Publishing Group
Subjects
Apoptosis
Bone marrow
Bone mass
Cartilage
Cell Differentiation - genetics
Chondrocytes
Chondrocytes - metabolism
Chondrogenesis
Dwarfism
Gene expression
Glycolysis
Glycolysis - genetics
Growth plate
Growth Plate - metabolism
Hospitals
Hypoxia
Laboratory animals
Metabolism
Orthopedics
Post-transcription
RNA, Messenger - metabolism
Skeletogenesis
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Summary: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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ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-022-05239-0