Multi-Omics Integration Identifies PTGS2 as a Candidate Diagnostic Biomarker and Precise Therapeutic Target Related...

Currently, there is a lack of effective disease-modifying drugs for osteoarthritis (OA), and existing treatment methods often accompany significant adverse reactions. Schisandra chinensis (SC), as a traditional Chinese medicine with anti-inflammatory activity, may have therapeutic potential for OA, but its specific molecular mechanism is not yet clear. This study adopts network pharmacology strategy to explore the potential mechanism of SC intervention in OA. Screen SC active ingredients through TCMSP database and obtain OA-related targets by combining OMIM, TTD, and GeneCards databases. Venn analysis shows that there are only 5 common targets between SC and OA; Further analysis revealed that PTGS2 is the only candidate target with diagnostic value (AUC = 0.702, p = 0.015), while AR, ESR1, DPP4, and CHRM2 did not show clinical diagnostic efficacy. Functional enrichment analysis suggests that common targets mainly involve steroid hormone responses and extracellular matrix (ECM) related pathways, with a significant enrichment in "response to steroid hormones" (adjusted p = 1.2 × 10 ^-5), and GSEA also shows activation of the ECM-receptor interaction pathway (NES = 1.87, p = 0.002). The molecular docking results indicate that the SC active ingredients MOL008957 and MOL008978 can form stable binding with PTGS2. The qRT-PCR results further confirmed that the expression of PTGS2 was significantly downregulated in the OA model after SC intervention. Single cell transcriptome analysis showed that PTGS2 was mainly enriched in monocytes and gradually increased with the pseudo temporal progression; Cell communication analysis revealed that monocytes can interact with NK cells and T cells through the MIF-CD74 + CXCR4 and MIF-CD74 + CD44 signaling axes. After virtual knockout of PTGS2, downstream regulatory networks suggest that GSN may be a key target gene, mainly involving collagen containing extracellular matrix and ECM structural components. In summary, SC may exert its anti OA effect mainly by selectively inhibiting PTGS2 and maintaining the homeostasis of ECM related pathways. PTGS2 is expected to become a candidate biomarker for OA and a potential target for SC intervention in OA, but further experimental verification of the specific efficacy and mechanism of SC active ingredients is still needed.