Underlying mechanism of B6D/M‐facilitated chondrogenesis by RNA‐Seq. A) The number of significantly regulated genes (≥2‐fold difference: upregulated (green arrow) and downregulated (purple arrow)) for bone formation and immune biological process. B) A heatmap of significantly differentially expressed mRNA levels related to chondrogenesis. C) Protein expression of Hif‐3α, SOX5, FOXO1, FOXO3a, SOX9, COL 2 analyzed by Western blotting. D) Different cell behaviors on B/M and B6D/M. Pro‐inflammation microenvironment in B/M‐initiated DNA damage and immunomodulation capability. Tailored immune microenvironment by B6D/M activated Hif‐3α, thereafter stimulated FOXO signaling pathway and SOX5, then upregulated SOX9, and ultimately initiated the development of COL 2 indicating rapid chondrogenic differentiation of MSCs. (*p < 0.05, N = 3.)