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Background <p>Tissue engineering technology has limited application in bone tissue regeneration because the mechanism remains unclear. SUV39H1 is a well-characterized histone methyltransferase, but its specific role in bone regeneration of dental pulp stem cells(DPSCs) remains unclear. Mitochondrial energy metabolism plays a regulatory role in osteogenesis, with lipid metabolites serving as critical substrates to fuel this process. FASN has been established as a key regulator of fatty acid metabolism. Therefore, we speculate that SUV39H1 influences the osteogenic differentiation of DPSCs through the mediation of FASN. However, it is still unclear how to regulate the expression of the SUV39H1.</p> Methods <p>Alkaline phosphatase activity and alizarin red staining were used to detect the osteogenic differentiation of DPSCs. Real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot were performed to detect gene expression levels. Cranioparietal bone replantation in rats and subcutaneous replantation in nude mice were used to confirm bone tissue regeneration. The Seahorse Cell Mitochondria Stress Test was used to detect the oxygen consumption rate. Co-Immunoprecipitation and GST pull-down confirmed the proteins complex. Lipid metabolism sequencing was used to detect the lipid metabolites. Software-based prediction tools analyze gene conservation and interaction networks. Dual-luciferase Reporter Gene Assay was used to detect SUV39H1 regulation by miRNA.</p> Results <p>SUV39H1 promoted osteogenic differentiation and bone regeneration in DPSCs. Our results further demonstrated that SUV39H1 enhanced the osteogenic differentiation of DPSCs by promoting lipid metabolism and subsequent mitochondrial energy metabolism. Upon exploring the mechanism by which SUV39H1 regulates lipid metabolism and mitochondrial function. SUV39H1 was found to bind to non-histone and methylated FASN. Simultaneously, FASN was degraded by ubiquitination after SUV39H1 combined with FASN. Thus, SUV39H1 was speculated to methylate FASN, and subsequently recruit a ubiquitination enzyme targeting FASN for degradation. This process modulated lipid and mitochondrial energy metabolism to facilitate the bone regeneration of DPSCs. Regarding the mechanism of regulating SUV39H1 expression, miR-4788 bound to the 3 ‘UTR of SUV39H1 was found to silence its expression.</p> Conclusion <p>Overall, SUV39H1 facilitated the osteogenic differentiation of DPSCs by modulating lipid metabolism and affected mitochondrial energy metabolism through FASN via non-histone methylation and ubiquitination mechanisms. The expression of SUV39H1was regulated by miR-4788.</p>

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SUV39H1 facilitate the osteogenic differentiation of dental pulp stem cells by modulating lipid metabolism and mitochondrial dynamics through FASN via non-histone methylation and ubiquitination mechanism

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月25日

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  • Ning Wang,
  • Wanqing Wang,
  • Xiao Han,
  • Yangyang Cao,
  • Haoqing Yang,
  • Chen Zhang,
  • Huina Liu,
  • Mengyuan Zhu,
  • Dengsheng Xia,
  • Zhipeng Fan

摘要

Background

Tissue engineering technology has limited application in bone tissue regeneration because the mechanism remains unclear. SUV39H1 is a well-characterized histone methyltransferase, but its specific role in bone regeneration of dental pulp stem cells(DPSCs) remains unclear. Mitochondrial energy metabolism plays a regulatory role in osteogenesis, with lipid metabolites serving as critical substrates to fuel this process. FASN has been established as a key regulator of fatty acid metabolism. Therefore, we speculate that SUV39H1 influences the osteogenic differentiation of DPSCs through the mediation of FASN. However, it is still unclear how to regulate the expression of the SUV39H1.

Methods

Alkaline phosphatase activity and alizarin red staining were used to detect the osteogenic differentiation of DPSCs. Real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot were performed to detect gene expression levels. Cranioparietal bone replantation in rats and subcutaneous replantation in nude mice were used to confirm bone tissue regeneration. The Seahorse Cell Mitochondria Stress Test was used to detect the oxygen consumption rate. Co-Immunoprecipitation and GST pull-down confirmed the proteins complex. Lipid metabolism sequencing was used to detect the lipid metabolites. Software-based prediction tools analyze gene conservation and interaction networks. Dual-luciferase Reporter Gene Assay was used to detect SUV39H1 regulation by miRNA.

Results

SUV39H1 promoted osteogenic differentiation and bone regeneration in DPSCs. Our results further demonstrated that SUV39H1 enhanced the osteogenic differentiation of DPSCs by promoting lipid metabolism and subsequent mitochondrial energy metabolism. Upon exploring the mechanism by which SUV39H1 regulates lipid metabolism and mitochondrial function. SUV39H1 was found to bind to non-histone and methylated FASN. Simultaneously, FASN was degraded by ubiquitination after SUV39H1 combined with FASN. Thus, SUV39H1 was speculated to methylate FASN, and subsequently recruit a ubiquitination enzyme targeting FASN for degradation. This process modulated lipid and mitochondrial energy metabolism to facilitate the bone regeneration of DPSCs. Regarding the mechanism of regulating SUV39H1 expression, miR-4788 bound to the 3 ‘UTR of SUV39H1 was found to silence its expression.

Conclusion

Overall, SUV39H1 facilitated the osteogenic differentiation of DPSCs by modulating lipid metabolism and affected mitochondrial energy metabolism through FASN via non-histone methylation and ubiquitination mechanisms. The expression of SUV39H1was regulated by miR-4788.