Molecular signaling in bone fracture healing and distraction osteogenesis

The process of fracture healing has been described in detail in many histol ogical studies. Recent work has focused on the mechanisms by which growth a nd differentiation factors regulate the fracture healing process. Rapid pro gress in skeletal cellular and molecular biology has led to the identificat ion of many signaling molecules associated with the formation of skeletal t issues, including members of the transforming growth factor-beta (TGF-beta) superfamily and the insulin-like growth factor (IGF) family. Increasing ev idence indicates that they are critical regulators of cellular proliferatio n, differentiation, extracellular matrix biosynthesis and mineralization. L imb lengthening procedure (distraction osteogenesis) is a relevant model to investigate the in vivo correlation between mechanical stimulation and bio logical responses as the callus is stretched by a proper rate and rhythm of mechanical strain. This model also provides additional insights into the m olecular and cellular events during bone fracture repair. TGF-beta 1 was si gnificantly increased in both the distracted callus and the fracture callus . The increased level of TGF-beta 1, together with a low concentration of c alcium and an enhanced level of collagen synthesis, was maintained in the d istracted callus as long as mechanical strain was applied. Less mineralizat ion is also associated with a low level of osteocalcin production. These ob servations provide further insights into the molecular basis for the cellul ar events during distraction osteogenesis.