Delayed Bone Wound Healing in Cbfa1-Deficient Mice

The core binding factor 1 (Cbfa1), more recently termed Runx2, is a "master gene" required for osteoblastic differentiation. Cbfa1 is expressed early in mesenchymal and epithelial elements destined to form the mineralized tissues of the tooth and periodontal apparatus. Objectives: To test the hypothesis that tissue repair and bone regeneration are compromised in Cbfa1+/- mice. Methods: Periodontal and femur bone defects (1 and 2 mm in dia., respectively) in 4 Cbfa1+/- mice, were generated with a dental bur driven by a slow speed handpiece. Same surgical procedure was performed in 4 normal mice that served as controls. The animals were killed 2 and 3 weeks after wounding, respectively. Defined tissue samples encompassing the defects were dissected and processed for histological examination. Results: It was found that alveolar bone defects healed in wild type mice. The newly formed bone showed a trabecular structure, and the bone was well mineralized and merged with the normal bone at the defect edges. In contrast, 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 alveolar bone defects were largely filled with fibrous connective tissues 3 weeks after surgery. The bone wounds in femurs in normal mice showed callus formation at the inner side. In some cases the defects almost healed completely. In Cbfa1+/- mice the repair occurred at a much slower pace and granulation tissue was seen at the wound sites. In some cases the femur wound was still widely open without any significant bone formed. Conclusions: The reduced expression of Cbfa1 interferes with the process of bone wound healing, and suggest the involvement of Cbfa1 in the control of differentiation of bone repairing cells and possible subsequent bone matrix formation and mineralization. Supported by NIDCR grant R01DE11088-6.