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<p>Knee trauma is an important risk factor for post-traumatic osteoarthritis (PTOA), a progressive joint disease characterized by articular cartilage degeneration and limited disease-modifying treatment options. Matrix metalloproteinase-13 (MMP-13/collagenase-3) contributes to cartilage extracellular matrix degradation through cleavage of type II collagen, making it a relevant molecular target for cartilage-protective drug discovery. This study aimed to identify and prioritize potential small-molecule MMP-13 inhibitors using an integrated in silico workflow. The workflow included MMP-13 sequence retrieval, structural characterization, pharmacophore-based screening, molecular docking, ADMET/toxicity prediction, protein-ligand interaction analysis, protein-protein interaction and co-expression network analysis, and 100 ns molecular dynamics simulation. Among the screened compounds, P4C-BM was prioritized as an early-stage computational lead candidate based on its combined docking score, predicted ADMET profile, interaction pattern, and molecular dynamics stability. However, the findings are preliminary and computational only. The present study does not experimentally demonstrate direct MMP-13 inhibition, selectivity against other MMP family members, cartilage repair, clinical efficacy, or synergy with platelet-rich plasma, physiotherapy, or other treatment modalities. Among the screened compounds, P4C-BM was prioritized as an early-stage computational lead candidate based on its combined docking score, predicted ADMET profile, interaction pattern, and molecular dynamics stability. However, the findings are preliminary and computational only. The present study does not experimentally demonstrate direct MMP-13 inhibition, selectivity against other MMP family members, cartilage protection, cartilage repair, disease modification, or clinical efficacy. Therefore, P4C-BM should be regarded only as a candidate for further experimental validation in enzymatic assays, chondrocyte models, cartilage explant studies, and in vivo osteoarthritis or post-traumatic osteoarthritis models. No practice-related or treatment recommendations can be made from the present data.</p>

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In silico prioritization of potential matrix metalloproteinase-13 inhibitors for cartilage degeneration in knee injury-associated osteoarthritis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月22日

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  • Aijuan Zhang,
  • Hongmei Chen,
  • Na Song,
  • Juanjuan Zhuang,
  • Baochai Chen,
  • Xiuying Lin,
  • Shuang Jin,
  • Chen Chen

摘要

Knee trauma is an important risk factor for post-traumatic osteoarthritis (PTOA), a progressive joint disease characterized by articular cartilage degeneration and limited disease-modifying treatment options. Matrix metalloproteinase-13 (MMP-13/collagenase-3) contributes to cartilage extracellular matrix degradation through cleavage of type II collagen, making it a relevant molecular target for cartilage-protective drug discovery. This study aimed to identify and prioritize potential small-molecule MMP-13 inhibitors using an integrated in silico workflow. The workflow included MMP-13 sequence retrieval, structural characterization, pharmacophore-based screening, molecular docking, ADMET/toxicity prediction, protein-ligand interaction analysis, protein-protein interaction and co-expression network analysis, and 100 ns molecular dynamics simulation. Among the screened compounds, P4C-BM was prioritized as an early-stage computational lead candidate based on its combined docking score, predicted ADMET profile, interaction pattern, and molecular dynamics stability. However, the findings are preliminary and computational only. The present study does not experimentally demonstrate direct MMP-13 inhibition, selectivity against other MMP family members, cartilage repair, clinical efficacy, or synergy with platelet-rich plasma, physiotherapy, or other treatment modalities. Among the screened compounds, P4C-BM was prioritized as an early-stage computational lead candidate based on its combined docking score, predicted ADMET profile, interaction pattern, and molecular dynamics stability. However, the findings are preliminary and computational only. The present study does not experimentally demonstrate direct MMP-13 inhibition, selectivity against other MMP family members, cartilage protection, cartilage repair, disease modification, or clinical efficacy. Therefore, P4C-BM should be regarded only as a candidate for further experimental validation in enzymatic assays, chondrocyte models, cartilage explant studies, and in vivo osteoarthritis or post-traumatic osteoarthritis models. No practice-related or treatment recommendations can be made from the present data.