Effects of Calcitonin Gene-Related Peptide on the Expression and Activity of Nitric Oxide Synthase During Mandibular Bone Healing in Rabbits: An Experimental Study

Purpose: Previous studies have found that calcitonin gene-related peptide (CGRP) takes part in the local regulation of bone growth and metabolism. However, the detailed regulatory mechanism of CGRP in the bone healing has not been explored. The objective of this study was to investigate the effects and the regulatory mechanism of CGRP on the expression and activity of nitric oxide synthase (NOS) in bony callus during mandibular defect healing. Materials and Methods: To determine the effect of CGRP on bony callus, a bone defect in the left mandible was created in 48 adult rabbits (divided randomly into experimental and control group) and half of them underwent inferior alveolar nerve amputation. The bony callus were collected 4, 7, 14, and 28 clays after operation, and the expressions of CGRP and NOS in the paraffin slices were analyzed with immunohistochemical staining. The activity of calcium-dependent nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) in the fresh specimens were measured with the NOS detecting kit. Results: In the immunohistochemcial analysis of bony callus, the immunohistochemical stain of CGRP was lower in experimental groups than in control groups from 4 to 14 days (P <.05 or P <.01), and the stain of cNOS showed the same phenomena from 4 to 7 days (P <.01), but the stain of iNOS did not show any statistical difference. In the NOS activity analysis, the activity of cNOS was lower in experimental groups than in control groups from 4 to 7 clays (P <.05 or P <.01), and the activity of iNOS was lower in experimental groups than in control groups from 7 to 14 days (P <.01). Conclusion: The expression and activity of NOS has a positive correlation with CGRP expression during bone healing. CGRP may promote fracture healing via regulating the expression and the activity of NOS. (C) 2009 American Association of Oral and Maxillofacial Surgeons