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Background <p>This study aimed to elucidate key molecular alterations in the osteoarthritis (OA) synovial microenvironment through transcriptomic analysis and to investigate the multi-target mechanisms of ShenTong ZhuYu Tang (STZYT) using network pharmacology and molecular docking.</p> Methods <p>We systematically integrated microarray data from OA synovial tissue available in the Gene Expression Omnibus (GEO) database. An integrated bioinformatics approach, including differential expression analysis, weighted gene co-expression network analysis (WGCNA), immune infiltration profiling, and machine learning, was employed to identify core genes and pathways. Subsequently, a network pharmacology analysis was conducted to construct an herb-compound-target-disease network and elucidate the potential mechanism of action of STZYT. Molecular docking was performed to validate the interaction between key STZYT compounds and matrix metalloproteinase-9 (MMP-9).</p> Results <p>A total of 294 differentially expressed genes (DEGs) were identified. Enrichment analysis revealed that these DEGs were significantly involved in inflammatory response and immune regulatory processes, as well as the pathways of osteoclast differentiation, NF-kappa B signaling, and IL-17 signaling. WGCNA and protein-protein interaction network analysis identified 51 hub genes. Subsequently, four machine learning algorithms further refined these to five key diagnostic biomarker candidates (CD4, MMP9, TNFSF11, CX3CR1, and EIF5B). Immune infiltration analysis showed significant infiltration of CD4 + T cells and M2-polarized macrophages. Network pharmacology identified 79 active STZYT compounds and 22 OA-related targets, suggesting the formula acts by inhibiting inflammation, metalloproteinase activity, and fibrosis. Molecular docking studies confirmed that quercetin, luteolin, and baicalein exhibit strong binding affinity to MMP-9.</p> Conclusions <p>Elevated MMP expression, particularly of MMP-9, in synovial tissue is closely associated with OA progression. STZYT may exert therapeutic effects against OA through multi-target mechanisms, including suppressing inflammation, inhibiting metalloproteinases, and preventing synovial fibrosis.</p>

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Synovial transcriptome analysis reveals ShenTong ZhuYu Tang alleviates osteoarthritis by targeting MMP-9 and immune microenvironment

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月16日

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  • Tihong Liang,
  • Bo Zhou,
  • Changwen Gu,
  • Guoxuan Peng,
  • Xu Ning,
  • Mingzhi Huang

摘要

Background

This study aimed to elucidate key molecular alterations in the osteoarthritis (OA) synovial microenvironment through transcriptomic analysis and to investigate the multi-target mechanisms of ShenTong ZhuYu Tang (STZYT) using network pharmacology and molecular docking.

Methods

We systematically integrated microarray data from OA synovial tissue available in the Gene Expression Omnibus (GEO) database. An integrated bioinformatics approach, including differential expression analysis, weighted gene co-expression network analysis (WGCNA), immune infiltration profiling, and machine learning, was employed to identify core genes and pathways. Subsequently, a network pharmacology analysis was conducted to construct an herb-compound-target-disease network and elucidate the potential mechanism of action of STZYT. Molecular docking was performed to validate the interaction between key STZYT compounds and matrix metalloproteinase-9 (MMP-9).

Results

A total of 294 differentially expressed genes (DEGs) were identified. Enrichment analysis revealed that these DEGs were significantly involved in inflammatory response and immune regulatory processes, as well as the pathways of osteoclast differentiation, NF-kappa B signaling, and IL-17 signaling. WGCNA and protein-protein interaction network analysis identified 51 hub genes. Subsequently, four machine learning algorithms further refined these to five key diagnostic biomarker candidates (CD4, MMP9, TNFSF11, CX3CR1, and EIF5B). Immune infiltration analysis showed significant infiltration of CD4 + T cells and M2-polarized macrophages. Network pharmacology identified 79 active STZYT compounds and 22 OA-related targets, suggesting the formula acts by inhibiting inflammation, metalloproteinase activity, and fibrosis. Molecular docking studies confirmed that quercetin, luteolin, and baicalein exhibit strong binding affinity to MMP-9.

Conclusions

Elevated MMP expression, particularly of MMP-9, in synovial tissue is closely associated with OA progression. STZYT may exert therapeutic effects against OA through multi-target mechanisms, including suppressing inflammation, inhibiting metalloproteinases, and preventing synovial fibrosis.