Subchondral injection of human umbilical cord mesenchymal stem cells ameliorates knee osteoarthritis by inhibiting osteoblast apoptosis and TGF-beta activity

• Subchondral injection of UCMSCs significantly improves trabecular microarchitecture (Tb.Sp, Tb.N) in OA rats, outperforming intra-articular injection in these specific parameters. • Both subchondral and intra-articular UCMSC injections effectively preserve cartilage, synovium, and subchondral bone, and promote osteoblastic bone formation while reducing aberrant angiogenesis. • The therapeutic mechanism involves inhibition of excessive TGF-β/pSmad2 signaling, which in turn reduces osteoblast apoptosis and restores bone remodeling balance. • Subchondral delivery of MSCs represents a promising, potentially superior route for treating OA by directly targeting subchondral bone pathology.