Identification of target genes of Astragalus mongholicus and Saposhnikovia divaricata extracts in human synoviocytes for potential osteoarthritis treatment.

Osteoarthritis (OA) is a leading cause of pain and disability worldwide. Despite extensive research, no curative treatment is currently available. Most therapies focus on symptom relief or disease modification. Traditional Chinese medicines, particularly Astragalus mongholicus (Huangqi) and Saposhnikovia divaricata (Fangfeng), have demonstrated therapeutic potential for OA, but their molecular mechanisms remain unclear. The synovium plays a key role in OA pathogenesis and disease progression, yet the effects of these herbal extracts on synoviocytes are poorly understood. To explore potential targets, we analyzed all publicly available microarray datasets comparing gene expression in OA and healthy synovium/synoviocytes. Differentially expressed genes (DEGs) were identified and compared with known targets of A. mongholicus and S. divaricata. The intersecting genes were subjected to Gene Ontology, KEGG pathway, and protein‒protein interaction analyses to identify hub genes. Key transcription factors were predicted using the KNOCK.TF database. Expression of hub genes and transcription factors was validated in human synoviocytes treated with A. mongholicus and S. divaricata extracts. We identified ten hub genes, eight of which may serve as OA biomarkers. Three hub transcription factors—AR, CITED2, and SF1—were upregulated by the extracts, while MMP2 and MMP9, two OA-associated genes, were downregulated. Our findings suggest that A. mongholicus and S. divaricata may exert therapeutic effects on OA by modulating synoviocyte gene expression, notably through upregulation of AR and CITED2 and downregulation of MMP2 and MMP9. These herbs may provide molecular targets for novel OA treatments.