Fig. 4: Senolytics counteracts the accelerated cavarial defect healing induced by sympathetic nerve inhibition.

A Lollipop plot showing signaling pathways in monocytes/macrophages in both the 6-OHDA treatment group and the PBS treatment group at day 14 post-defect. B GSEA analysis revealing the enrichment of lysosome signaling pathway in monocytes/macrophages in the 6-OHDA treatment group at day 14 post-defect. C Violin plot showing the lysosome gene set scores in monocytes/macrophages in both the 6-OHDA treatment group and the PBS treatment group at day 14 post-defect. D GSEA analysis revealing the enrichment of aging pathway in monocytes/macrophages in the 6-OHDA treatment group at day 14 post-defect. E SA-β-gal staining of calvarial bone from PBS or 6-OHDA treatment mice. Scale bar, 50 μm. F Flow cytometry showing the percentage of senescent cells from PBS or 6-OHDA treatment mice. G Quantification of senescent cells by flow cytometry in PBS- and 6-OHDA-treated groups. H Micro-CT reconstructions of the defect site in a top-down view and H&E stain of representative coronal cross-section of the healing defect site among animals treated with PBS, D/Q, 6-OHDA or 6-OHDA + D/Q, (D/Q indicates senolytics Dasatinib and Quercetin). Analysis performed at day 28 post-defect. Margins of original defect are indicated by dashed red lines. Scale bar, 500 μm. Micro-CT quantification of bone healing, among PBS, D/Q, 6-OHDA and 6-OHDA + D/Q treatment mice, including I bone volume/tissue volume (BV/TV) and J relative area of bone defect. K Workflow illustrating the process of senescent cell sorting and transplantation (Created in BioRender. Bian, Z. (2025) https://BioRender.com/t10k902). L Micro-CT reconstructions of the defect site in a top-down view and H&E stain of representative coronal cross-section of the healing defect site among animals treated with PBS or senescent cells. Analysis performed at day 28 post-defect. Margins of original defect are indicated by dashed red lines. Scale bar, 500 μm. Micro-CT quantification of bone healing, among PBS and senescent cells treatment mice, including M bone volume/tissue volume (BV/TV) and N relative area of bone defect.