Signaling pathways | Major characteristics and functions | Applications in bone regeneration |
---|---|---|
BMP-2 | BMP-2 initially binds to type II receptors on the cell membrane and then binds to type I receptors to form a dimer. The activated type I receptors rapidly phosphorylate the serine residues of SMAD-1, SMAD-5, and SMAD-8, and the activated SMADs are transferred into the nucleus and exert biological effects [35, 36] | The osteoporotic phenotype was reversed in mice with systematic injections of rhBMP-2 [35] MSCs infected with a recombinant adenoviral vector encoding human BMP-2 were capable of repairing bone defects in ectopic sites through engrafting and forming bone and cartilage in mice [36, 37] 3D bioprinted implants containing a VEGF gradient, paired with spatially defined BMP-2 localization and release kinetics, expedited the healing of defects in large bone with the minuscule formation of heterotopic bone [38] mRNA-based BMP-2 therapy was used to facilitate bone regeneration in mice [39,40,41] |
NGF-p75 signaling | Cranial bone injuries stimulate NGF expression and its signals via p75 in resident osteogenic precursors that affect their migration into the damaged tissue and promote bone regeneration [42] | NGF-p75 signaling pathway coordinates skeletal cell migration during early bone repair [42] |
FAK | Mechanotransduction via the FAK signaling pathway in skeletal stem cells promotes stem-cell-mediated regeneration of adult skeletal tissue [43, 44] | Inhibiting FAK abolishes bone regeneration in distraction osteogenesis [44] |
NF-κB | Activation of NF-κB signaling in osteoclasts is crucial for their differentiation and activation, whereas the activation in osteoblasts inhibits bone formation. These unique characteristics imply the great potential of NF-κB as a therapeutic target for bone disorders and regeneration [45] | The activating NF-κB signaling may be one of the extrinsic mechanisms by which skeletal stem cell function decline during human skeletal aging [45,46,47,48,49] |