Fig. 5

The ANXA2/CTGF-TSP1 complex is responsible for the invasion and migration of RA FLS in the SCID model. Cartilage graft injected with the FLS (treated as methods above) was transplanted into SCID mice (n = 10 mice per group). A The schematic protocol for the FLS-cartilage-SCID model (arrow depicts the site of transplants.) B H&E staining of the cartilage removed from SCID mice with a magnification of × 200. The arrows indicate RA FLS invaded into the cartilage. C Measurement of invasion of RA FLS into human cartilage implants transferred under the skin of SCID mice. The level of invasiveness was scored as follows: 0 = no or minimal invasion, 1 = visible invasion (two-cell depth), 2 = invasion (five-cell depth), and 3 = deep invasion (more than ten-cell depth). The sections were examined by two experienced scientists in a blinded manner. D H&E staining of the knee joints of the SCID mice (original magnification, up × 40 and down × 100). E Histological scores for synovial infiltration, synovial hyperplasia, and cartilage and bone damage were assessed and graded on a scale of 0 (normal) to 3 (severe). F Interaction between the ANXA2 and TSP1 domain of CTGF forces FLS migration and pannus formation in the RA process