Involvement of TGFβ/SMAD2 and Integrin β1/ERK Pathways in Chondrogenesis of CD105-ABBS-Bonded SMSCs Under Weight-Bearing In Vivo

Cartilage regeneration in weight-bearing areas is quite important, and the role of weight bearing on cartilage repair is unclear. We analyzed the effect of weight-bearing on chondrogenesis of CD105-avidin-biotin binding system (CD105-ABBS)-bonded synovial mesenchymal stem cells (SMSCs) and explored the underlying mechanisms. Cartilage defects in bilateral femoral condyles and intercondyle fossae of 4 beagles were created as the weight-bearing and non-weight-bearing areas, and scaffolds loaded with CD105-ABBS-bonded SMSCs were implanted. All the animals were sacrificed at week 6, and the distal femurs were harvested. Macroscopic observation showed limited cartilage formation in both areas, while hematoxylin and eosin staining detected better neocartilage regeneration in the weight-bearing area, and immunohistochemical and western blot analyses confirmed the better distribution of collagen II and aggrecan and lower level of matrix metallopeptidase 13 in weight-bearing areas compared with non-weight-bearing areas. Meanwhile, the expression levels of pSMAD2, integrin beta 1, and pERK were much higher in the weight-bearing areas. This study demonstrated that physiological weight bearing regulate the CD105-ABBS-bonded SMSCs towards chondrogenesis. Further, the underlying mechanism may be related to the feedback loop between TGF beta/SMAD2 and integrin beta 1/ERK as SMAD2 may inhibit the ERK-related hypertrophy, and ERK may promote the SMAD2-driven chondrogenesis, and this requires further confirmation.