Pediatric Fracture Remodeling: From Wolff to Wnt.

Pediatric fracture remodeling is a complex mechanobiological process in which a team of cells, including osteoclasts, osteoblasts, and osteocytes, responds to cytokine and mechanical signals to synthesize new bone in areas of high stress (concavity of a fracture) and remove older redundant bone in areas of low stress (convexity and medullary canal). Piezo1 mechanoreceptors and other pressure-sensitive membrane proteins perceive and convert mechanical strains into intracellular chemical signals. Cytokines are peptides that bind to cell membrane receptors and influence cell functions. Bone morphogenetic proteins and Wnt are the major osteogenic cytokines. Macrophage colony-stimulating factor and receptor activator of nuclear factor κB ligand (RANKL) are the major osteoclastic cytokines. The combination of mechanical stresses and cytokine concentrations stimulates osteoclasts to resorb bone and osteoblasts to make new bone, resulting in remodeling that restores bone strength and structure.