2. Academic Validation
  3. Hnrnpk maintains chondrocytes survival and function during growth plate development via regulating Hif1α-glycolysis axis

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

  • Cell Death Dis. 2022 Sep 20;13(9):803. doi: 10.1038/s41419-022-05239-0.
Yuyu Chen  # 1,  Jinna Wu  # 2,  Shun Zhang  # 1,  Wenjie Gao 3,  Zhiheng Liao 1,  Taifeng Zhou 1,  Yongyong Li 4,  Deying Su 5,  Hengyu Liu 1,  Xiaoming Yang 6,  Peiqiang Su 7,  Caixia Xu 8
Affiliations

Affiliations

  • 1 Department of Spine Surgery, Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
  • 2 Department of Breast Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510095, China.
  • 3 Department of Orthopaedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China.
  • 4 Precision Medicine Institute, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
  • 5 Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • 6 Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • 7 Department of Spine Surgery, Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China. [email protected].
  • 8 Research Center for Translational Medicine, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China. [email protected].
  • # Contributed equally.
PMID: 36127325 DOI: 10.1038/s41419-022-05239-0
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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