Fig. 5

Possible schematic diagram of NF-κB signalling during osteogenesis of endochondral ossification. A Macroscopic scheme of the general process of osteogenesis. MSCs condense into osteoprogenitors. Then, osteoprogenitors differentiate into osteoblasts. Finally, osteoblasts mature into osteocytes. B The left osteoblast: During osteogenesis, SPARC expression is decreased and can activate the phosphorylation of MAPK, which might induce NF-κB signalling to initiate osteogenic expression. However, on the one hand, BMP could promote osteoblast differentiation via smad signalling. On the other hand, BMP-mediated signalling may promote NF-κB activity via PI3K/AKT/mTOR axis where P65 may inhibit smad signalling to induce Runx2 expression and activity to block osteoblast differentiation. The right osteoblast: mechanical stress may activate mTOR signalling via AKT activation or integrin-mediated FAK signalling to further induce P50/P65 which could promote proinflammatory gene expression including IL-1β and TNF-α. Additionally, P50/P65 could also inhibit smad activity induced by BMP signalling to decrease osteoblast differentiation. Moreover, active P65 may inhibit JNK which could further repress Fra1 to dampen osteoblast activity (Created with BioRender.com)