When TNFR1 was blocked, the expression of COL2A1 and ACAN was partially impaired, but the effect of PGRN on Akt and Erk1/2 activation remained unchanged, when TNFR2 was blocked, the anabolic effect of PGRN was cancelled, and the effect of PGRN on Akt and Erk1/2 activation disappeared (147), indicating that PGRN inhibited the inflammatory response, increased bone formation, and promoted fracture healing in T2DM through the TNFR2, Akt, and Erk1/2 pathways (Figure 8B). This evidence concerns the gene COL2A1 and type 2 diabetes mellitus.