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Background <p>Periodontitis is a chronic inflammatory disease that affects the supporting tissues around teeth. A reduction in the pluripotency of periodontal ligament stem cells (PDLSCs) has been identified as a pivotal factor in age-related alveolar bone loss. This study investigated the effects of special AT-rich binding protein 1 (SATB1) on the osteogenic differentiation capacity of PDLSCs under H<sub>2</sub>O<sub>2</sub>-induced senescent conditions and its potential mechanisms, thereby providing new insights into periodontal regeneration in patients with periodontitis.</p> Methods <p>The osteogenic differentiation capacity of PDLSCs was determined by alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and western blotting. Co-immunoprecipitation (Co-IP) was used to detect the binding of SATB1 to histone deacetylase 1 (HDAC1) and a ubiquitination assay was employed to detect the protein stability of SATB1.</p> Results <p>Under normal and H<sub>2</sub>O<sub>2</sub>-stimulation conditions, SATB1 enhances osteogenic differentiation of PDLSCs by activating the p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) signaling pathways. The Co-IP results indicated that SATB1 could physically bind to HDAC1 and the binding of SATB1 and HDAC1 proteins decreased under H<sub>2</sub>O<sub>2</sub>-induced senescent conditions. In addition, HDAC1 promoted the expression of SATB1 and rescued the osteogenic differentiation capacity of PDLSCs via the activation of the p38 MAPK pathway under senescent conditions. Nevertheless, HDAC1 deacetylation mutant (HDAC1-H141A-MUT) did not affect the binding of SATB1 and HDAC1 but lost the effect of upregulating the expression of SATB1. Moreover, HDAC1-H141A-MUT lost the ability to promote the osteogenic differentiation of PDLSCs and the activation of the p38 MAPK signaling pathway. Furthermore, protein half-life experiments indicated that HDAC1 hindered the degradation of the SATB1 protein, whereas HDAC1-H141A-MUT lost this function. In the end, ubiquitination assay demonstrated that HDAC1 inhibited the ubiquitination of SATB1, while HDAC1-H141A-MUT has no effect on the ubiquitination of SATB1 protein.</p> Conclusions <p>SATB1 modulated the osteogenic differentiation of PDLSCs through HDAC1 mediated non-histone protein deacetylation and ubiquitination and through the p38 MAPK pathway under H<sub>2</sub>O<sub>2</sub>-induced senescence conditions. Therefore, this new mechanism provides a feasible strategy for promoting periodontal tissue regeneration.</p>

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SATB1 regulates the osteogenic differentiation of PDLSCs via HDAC1 mediated non-histone protein deacetylation and ubiquitination mechanism and through p38 MAPK pathway under hydrogen peroxide-induced senescent conditions

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月1日

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  • Meijun Hu,
  • Jiaxin Song,
  • Wanhao Yan,
  • Yu Jiang,
  • Chen Zhang,
  • Haoqing Yang,
  • Zhipeng Fan

摘要

Background

Periodontitis is a chronic inflammatory disease that affects the supporting tissues around teeth. A reduction in the pluripotency of periodontal ligament stem cells (PDLSCs) has been identified as a pivotal factor in age-related alveolar bone loss. This study investigated the effects of special AT-rich binding protein 1 (SATB1) on the osteogenic differentiation capacity of PDLSCs under H2O2-induced senescent conditions and its potential mechanisms, thereby providing new insights into periodontal regeneration in patients with periodontitis.

Methods

The osteogenic differentiation capacity of PDLSCs was determined by alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and western blotting. Co-immunoprecipitation (Co-IP) was used to detect the binding of SATB1 to histone deacetylase 1 (HDAC1) and a ubiquitination assay was employed to detect the protein stability of SATB1.

Results

Under normal and H2O2-stimulation conditions, SATB1 enhances osteogenic differentiation of PDLSCs by activating the p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) signaling pathways. The Co-IP results indicated that SATB1 could physically bind to HDAC1 and the binding of SATB1 and HDAC1 proteins decreased under H2O2-induced senescent conditions. In addition, HDAC1 promoted the expression of SATB1 and rescued the osteogenic differentiation capacity of PDLSCs via the activation of the p38 MAPK pathway under senescent conditions. Nevertheless, HDAC1 deacetylation mutant (HDAC1-H141A-MUT) did not affect the binding of SATB1 and HDAC1 but lost the effect of upregulating the expression of SATB1. Moreover, HDAC1-H141A-MUT lost the ability to promote the osteogenic differentiation of PDLSCs and the activation of the p38 MAPK signaling pathway. Furthermore, protein half-life experiments indicated that HDAC1 hindered the degradation of the SATB1 protein, whereas HDAC1-H141A-MUT lost this function. In the end, ubiquitination assay demonstrated that HDAC1 inhibited the ubiquitination of SATB1, while HDAC1-H141A-MUT has no effect on the ubiquitination of SATB1 protein.

Conclusions

SATB1 modulated the osteogenic differentiation of PDLSCs through HDAC1 mediated non-histone protein deacetylation and ubiquitination and through the p38 MAPK pathway under H2O2-induced senescence conditions. Therefore, this new mechanism provides a feasible strategy for promoting periodontal tissue regeneration.