4-aminobiphenyl (4-ABP) is found in cartilage after oral kartogenin (KGN) administration and promotes chondrogenic differentiation of cartilage-derived-stem/progenitor cells (CSPC). (A) Oral KGN administration schedule in destabilization of medial meniscus (DMM)-induced osteoarthritis in STR/Ort mice (a1). Representative images of toluidine blue and immunohistochemical staining of type II collagen and MMP-13 in articular cartilage (a2). Scale bars = 100 μm. OARSI score for osteoarthritis cartilage histopathological assessment (a3-a5). **p < 0.01, ***p < 0.001 versus sham; ##p < 0.01, ###p < 0.001 versus model. n = 5 per group. (B) HPLC/MS analysis of KGN and 4-ABP in blood (b1) and cartilage (b2) after 5 mg/kg KGN oral administration (OA) to STR/Ort mice. (C) CSPC were isolated from cartilage and treated with vehicle or 10 μM KGN, 4-ABP or phthalic acid (PA) in the chondrogenic differentiation medium. (D-F) Aggrecan, Sox9 and type II collagen mRNA expression levels (determined by RT-qPCR) at day 21. Pellet diameters (G) and their type II collagen expression (H) at day 21. *p < 0.05, **p < 0.01, ***p < 0.001 versus the vehicle group; #p < 0.05 versus the KGN group. n = 6 per group.