Cbfa1/Runx2-deficiency delays bone wound healing and locally delivered Cbfa1/Runx2 promotes bone repair in animal models

Core binding factor 1 (Cbfa1)/runt-related transcription factor 2 (Runx2) has been identified as a master gene in osteoblastic differentiation. In this two-part study, part I of the study was undertaken to test the hypothesis that bone regeneration is compromised in Cbfa1+/- mice. Compared with wild-type mice, wound healing was dramatically delayed in Cbfa1+/- mice characterized by the presence of a small amount of bone near the base of the wounds. The bone defects were largely filled with fibrous connective tissues 3 weeks after surgery. Part II was performed to determine the effects of Cbfa1 in enhancing bone wound healing using a gene-activated matrix (GAM) method. Cbfa1 cDNA was mixed with a biodegradable bovine type I collagen sponge and was inserted into the periodontal window wounds of mice. Control sponges were collagen matrix without Cbfa1 cDNA. Histological analysis and immunohistochemical staining demonstrated that compared with controls, there was increased new bone formation that almost filled the wound defects 14 days after surgery in the Cbfa1-GAM group. The collagen sponge matrix did not seem to elicit significant foreign body reaction in either group. In conclusion, the reduced expression of Cbfa1 interferes with the process of bone wound healing, and local application of Cbfa1 cDNA incorporated into a collagen matrix promotes bone tissue regeneration.