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Background <p>The development of the palate is a complex and continuous process, occurring in a series of stages with cartilage of being particular significance. Chondrogenesis is influenced by many factors such as metabolism, and hypoxia which are also risk factors for cleft palate. Hypoxia can increase the intracellular lactate levels due to increased glycolysis. However, the precise role of lactate in palatal cartilage development remains unclear.</p> Methods <p>Mouse embryonic palatal mesenchyme (MEPM) cells isolated from embryonic day 13.5 (E13.5) and E12.5 were obtained and characterized using immunofluorescence. Subsequently, following a 21-day induction culture in a chondrogenic medium, the MEPM cells were subjected to alcian blue staining and to quantitative real-time PCR to examine the ability of the cells to form a cartilage matrix under the influence of lactate, hypoxia, and a combination of both. The expression levels of glycolysis-related enzymes, hypoxia-inducible factor-1α (HIF-1α), and the phosphoinositide 3-kinase/AKT signaling pathway were examined using western blot and quantitative real-time PCR to investigate the mechanism of lactate in palatal cartilage development.</p> Results <p>The findings indicated that extracellular lactate supplementation impeded the formation of cellular cartilage matrix in comparison to the control group. Then hypoxia was observed to induce intracellular lactate accumulation and also inhibited the capacity of MEPM cells to form cartilage matrix. This process was associated with an increased expression of glycolysis-related enzymes and enhanced AKT signaling pathway activity.</p> Conclusions <p>This study demonstrates that lactate can inhibit palatal cartilage development and affect the process of glycolysis. Lactate inhibits palatal cartilage matrix formation by activating the AKT-PKM2 axis. This study contributes to our understanding of the role of lactate in palatal cartilage development. It provides a new direction for the etiology of cleft palate and a theoretical basis for its prevention and early intervention.</p>

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Lactate inhibits mouse embryonic palatal mesenchyme cells chondrogenesis through AKT-PKM2 axis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月31日

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  • Mingyue Meng,
  • Xige Zhao,
  • Xiaoyu Zheng,
  • Xiaotong Wang,
  • Xia Peng,
  • Zhiwei Wang,
  • Shiteng Wang,
  • Cui Guo,
  • Juan Du

摘要

Background

The development of the palate is a complex and continuous process, occurring in a series of stages with cartilage of being particular significance. Chondrogenesis is influenced by many factors such as metabolism, and hypoxia which are also risk factors for cleft palate. Hypoxia can increase the intracellular lactate levels due to increased glycolysis. However, the precise role of lactate in palatal cartilage development remains unclear.

Methods

Mouse embryonic palatal mesenchyme (MEPM) cells isolated from embryonic day 13.5 (E13.5) and E12.5 were obtained and characterized using immunofluorescence. Subsequently, following a 21-day induction culture in a chondrogenic medium, the MEPM cells were subjected to alcian blue staining and to quantitative real-time PCR to examine the ability of the cells to form a cartilage matrix under the influence of lactate, hypoxia, and a combination of both. The expression levels of glycolysis-related enzymes, hypoxia-inducible factor-1α (HIF-1α), and the phosphoinositide 3-kinase/AKT signaling pathway were examined using western blot and quantitative real-time PCR to investigate the mechanism of lactate in palatal cartilage development.

Results

The findings indicated that extracellular lactate supplementation impeded the formation of cellular cartilage matrix in comparison to the control group. Then hypoxia was observed to induce intracellular lactate accumulation and also inhibited the capacity of MEPM cells to form cartilage matrix. This process was associated with an increased expression of glycolysis-related enzymes and enhanced AKT signaling pathway activity.

Conclusions

This study demonstrates that lactate can inhibit palatal cartilage development and affect the process of glycolysis. Lactate inhibits palatal cartilage matrix formation by activating the AKT-PKM2 axis. This study contributes to our understanding of the role of lactate in palatal cartilage development. It provides a new direction for the etiology of cleft palate and a theoretical basis for its prevention and early intervention.