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Purpose <p>To investigate the impact of high glucose on the senescence of synovial mesenchymal stem cells (SMSCs) and to elucidate the role of mitochondrial dysfunction in this process.</p> Methods <p>‌SMSCs were treated with medium containing high glucose (25 mmol/L) or low glucose (5.5 mmol/L) concentrations. The effects of high glucose concentrations on the proliferation, senescence, mitochondrial reactive oxygen species (ROS) levels, mitochondrial fission, and mitophagy of SMSCs were investigated. First, the impact of 24-hour high glucose treatment on SMSCs was investigated‌. After this initial 24-hour exposure, the medium was subsequently changed to low glucose, and the cells were cultivated for an additional 24&#xa0;h; this was then compared with the effects of continuous 48-hour high-glucose exposure and continuous 48-hour low-glucose exposure.</p> Results <p>High glucose concentrations did not promote the proliferation of SMSCs but rather accelerated their senescence by ‌upregulating‌ the mRNA expression of senescence-associated secretory phenotype (SASP) genes and increasing the number of senescence-associated β-galactosidase (SA-β-gal)-positive cells. Additionally, high glucose ‌concentrations elevated‌ ROS levels in mitochondria and ‌facilitated‌ mitochondrial fission; they also ‌inhibited‌ the mitophagy of SMSCs by suppressing the expression of mitophagy-related proteins (PINK1, PARKIN, and LC3B). High glucose-induced suppression of mRNA (<i>Il-6</i>,<i> Cxcl1</i>,<i> Dnm1</i>,<i> Pink1</i>,<i> Prkn</i>,<i> Lc3b</i>) and protein (P21) expression, along with increased SA-β-gal-positive cell numbers and elevated MitoSOX intensity, can be reversed by terminating the high glucose treatment.</p> Conclusion <p>High glucose concentrations induce senescence in SMSCs via mitochondrial dysfunction, manifested as ROS accumulation, excessive fission, and mitophagy suppression. Glucose normalization reversed senescence phenotypes, accompanied by restored mitophagy and reduced oxidative stress. Mitochondrial dysfunction may be one of the key mechanisms underlying high glucose-induced senescence in SMSCs.</p>

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High glucose induces senescence in synovial mesenchymal stem cells through mitochondrial dysfunction

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月15日

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  • Shuyi Tan,
  • Wangxi Wu,
  • Yifan Chen,
  • Hai Gao

摘要

Purpose

To investigate the impact of high glucose on the senescence of synovial mesenchymal stem cells (SMSCs) and to elucidate the role of mitochondrial dysfunction in this process.

Methods

‌SMSCs were treated with medium containing high glucose (25 mmol/L) or low glucose (5.5 mmol/L) concentrations. The effects of high glucose concentrations on the proliferation, senescence, mitochondrial reactive oxygen species (ROS) levels, mitochondrial fission, and mitophagy of SMSCs were investigated. First, the impact of 24-hour high glucose treatment on SMSCs was investigated‌. After this initial 24-hour exposure, the medium was subsequently changed to low glucose, and the cells were cultivated for an additional 24 h; this was then compared with the effects of continuous 48-hour high-glucose exposure and continuous 48-hour low-glucose exposure.

Results

High glucose concentrations did not promote the proliferation of SMSCs but rather accelerated their senescence by ‌upregulating‌ the mRNA expression of senescence-associated secretory phenotype (SASP) genes and increasing the number of senescence-associated β-galactosidase (SA-β-gal)-positive cells. Additionally, high glucose ‌concentrations elevated‌ ROS levels in mitochondria and ‌facilitated‌ mitochondrial fission; they also ‌inhibited‌ the mitophagy of SMSCs by suppressing the expression of mitophagy-related proteins (PINK1, PARKIN, and LC3B). High glucose-induced suppression of mRNA (Il-6, Cxcl1, Dnm1, Pink1, Prkn, Lc3b) and protein (P21) expression, along with increased SA-β-gal-positive cell numbers and elevated MitoSOX intensity, can be reversed by terminating the high glucose treatment.

Conclusion

High glucose concentrations induce senescence in SMSCs via mitochondrial dysfunction, manifested as ROS accumulation, excessive fission, and mitophagy suppression. Glucose normalization reversed senescence phenotypes, accompanied by restored mitophagy and reduced oxidative stress. Mitochondrial dysfunction may be one of the key mechanisms underlying high glucose-induced senescence in SMSCs.