GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE317nnn/GSE317855/primaryOK200TranscriptomicsRattus norvegicusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317855GEOGSEfalseRat knee joint scRNA-seq data with meniscus injury treated by 4PPBPAvascular meniscus tears are a major contributor to mechanical joint locking, compromised gait and function, and the initiation and progression of post-traumatic osteoarthritis. Unfortunately, the avascular meniscus tears hardly heal. Here, we report a novel small molecule, 4-PPBP, a sigma-1 receptor (σ1R) agonist, exhibiting significant potential to promote avascular meniscus healing by activating synovial mesenchymal stem cells (syMSCs) and modulating macrophage-regulated inflammation via multi-tissue crosstalk. In vivo, a single injection of 4-PPBP-loaded bioglue minimized meniscal gapping, with improved meniscus healing and gait performance. In contrast to the degenerative changes in the untreated control, 4-PPBP/bioglue application resulted in integrated fibrocartilaginous tissues. scRNA-seq and CellChat analyses revealed 4-PPBP-activated cell-cell communications leading to inflammatory regulation and cell differentiation. Macrophages showed a robust reduction in pro-inflammatory genes, and fibroblasts, chondrocytes, and fibrochondrocytes increased genes associated with differentiation and matrix synthesis in response to 4-PPBP. Anti-inflammatory cell-cell communication signals were significantly elevated between adipocytes and macrophages.2026/04/14GSE317855GSM9480106GSM948010525947317855Rattus norvegicus