Cytokines and fracture healing

Fracture healing has been speculated to recapitulate the processes of skeletal embryogenesis; however, the occurrence of an early inflammatory response and associated up-regulated expression of pro-inflammatory cytokines makes fracture healing distinct. The pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) have been shown not only to coordinate the hematopoietic and immune systems, but also to contribute to bone repair by regulating osteoclastogenesis and the early recruitment and differentiation of osteoblastic lineage cells. Novel members of TNF/TNFR superfamily—RANKL, RANK, and OPG— were identified as the crucial factors in osteoclastogenesis and directly involved in the endochondral resorption and the remodeling phase of fracture healing. Further investigation into the roles and interactions of each of these cytokines is necessary for a better understanding of the normal and pathologic fracture healing and for the development of treatment tools to enhance it.