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<p>The pathogenesis of pulpitis remains unclear. This study sought to investigate the molecular mechanism by which the long noncoding RNA FOXD2-AS1 participates in pulpitis through regulating the miR-338-3p/<i>THBS1</i> axis. 110 irreversible pulpitis patients and 80 healthy orthodontic patients were enrolled as the pulpitis and control groups, respectively. Human dental pulp stem cells (hDPSCs) were cultured and stimulated with lipopolysaccharide (LPS) to establish a pulp inflammation model. Expression of FOXD2-AS1, miR-338-3p, and <i>THBS1</i> was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay, while levels of inflammatory cytokines and osteogenesis-related proteins were measured by enzyme-linked immunosorbent assay (ELISA). THBS1 protein expression was validated by Western blot. The target regulation was verified by RNA immunoprecipitation (RIP) and dual luciferase reporter assays. In pulpitis tissues, FOXD2-AS1 and <i>THBS1</i> expression were significantly upregulated, while miR-338-3p expression was significantly downregulated. Furthermore, FOXD2-AS1 demonstrated high diagnostic value for pulpitis. Functional experiments demonstrated that FOXD2-AS1 negatively regulated osteoblast differentiation and promoted LPS-induced inflammatory responses. Specifically, it inhibited alkaline phosphatase (ALP) activity and odontogenic differentiation-related protein expression, reduced cell viability, and promoted inflammatory cytokine release. Moreover, FOXD2-AS1 targeted and adsorbed miR-338-3p, while miR-338-3p directly targeted and inhibited <i>THBS1</i> expression, forming the FOXD2-AS1/miR-338-3p/<i>THBS1</i> regulatory axis. Rescue experiments demonstrated that knocking down FOXD2-AS1 exerted anti-inflammatory and pro-osteogenic effects by upregulating miR-338-3p and inhibiting <i>THBS1</i>. Conversely, inhibiting miR-338-3p reversed these protective effects, manifesting as exacerbated inflammation and diminished odontogenic differentiation capacity. On this basis, further knocking down THBS1 reinstates the anti-inflammatory and pro-osteogenic phenotype. In conclusion, FOXD2-AS1 mediates pulpitis inflammation and odontogenic differentiation imbalance by competitively binding to miR-338-3p to upregulate THBS1 expression.</p>

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Long non-coding RNA FOXD2-AS1 promotes inflammation but suppresses osteogenesis in pulpitis via miR-338-3p/THBS1 axis

  • 期刊论文

  • 发表日期：

    2026年6月22日

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  • Huawen Cui,
  • Yanmei Guo,
  • Yajun Zhang,
  • Hong Wang,
  • Meng Wu,
  • Zhengyi Chu,
  • Yang Yu

摘要

The pathogenesis of pulpitis remains unclear. This study sought to investigate the molecular mechanism by which the long noncoding RNA FOXD2-AS1 participates in pulpitis through regulating the miR-338-3p/THBS1 axis. 110 irreversible pulpitis patients and 80 healthy orthodontic patients were enrolled as the pulpitis and control groups, respectively. Human dental pulp stem cells (hDPSCs) were cultured and stimulated with lipopolysaccharide (LPS) to establish a pulp inflammation model. Expression of FOXD2-AS1, miR-338-3p, and THBS1 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay, while levels of inflammatory cytokines and osteogenesis-related proteins were measured by enzyme-linked immunosorbent assay (ELISA). THBS1 protein expression was validated by Western blot. The target regulation was verified by RNA immunoprecipitation (RIP) and dual luciferase reporter assays. In pulpitis tissues, FOXD2-AS1 and THBS1 expression were significantly upregulated, while miR-338-3p expression was significantly downregulated. Furthermore, FOXD2-AS1 demonstrated high diagnostic value for pulpitis. Functional experiments demonstrated that FOXD2-AS1 negatively regulated osteoblast differentiation and promoted LPS-induced inflammatory responses. Specifically, it inhibited alkaline phosphatase (ALP) activity and odontogenic differentiation-related protein expression, reduced cell viability, and promoted inflammatory cytokine release. Moreover, FOXD2-AS1 targeted and adsorbed miR-338-3p, while miR-338-3p directly targeted and inhibited THBS1 expression, forming the FOXD2-AS1/miR-338-3p/THBS1 regulatory axis. Rescue experiments demonstrated that knocking down FOXD2-AS1 exerted anti-inflammatory and pro-osteogenic effects by upregulating miR-338-3p and inhibiting THBS1. Conversely, inhibiting miR-338-3p reversed these protective effects, manifesting as exacerbated inflammation and diminished odontogenic differentiation capacity. On this basis, further knocking down THBS1 reinstates the anti-inflammatory and pro-osteogenic phenotype. In conclusion, FOXD2-AS1 mediates pulpitis inflammation and odontogenic differentiation imbalance by competitively binding to miR-338-3p to upregulate THBS1 expression.