Deferoxamine mesylate enhances mandibular advancement‐induced condylar osteogenesis by promoting H‐type angiogenesis

Abstract Background The effect of functional orthopaedic treatment for mandibular deficiency relies on mandibular advancement (MA)‐induced condylar new bone formation. However, this is not easy to achieve, especially in non‐growing patients. Therefore, how to obtain reliable MA‐induced condylar osteogenesis is a subject much worthy of study. Objective To investigate whether deferoxamine mesylate (DFM) enhances MA‐induced condylar osteogenesis in middle‐aged mice. Methods Forty 30‐week‐old male C57BL/6J mice were randomly divided into 4 groups: the control (Ctrl), DFM, MA + Ctrl and MA + DFM groups. After a 4‐week experimental period, femurs, tibias and condyles were collected for morphological, micro‐computed tomography and histological evaluation. Results For long bones, DFM reversed osteoporosis in middle‐aged mice by promoting H‐type angiogenesis. For mandibular condyles, MA promoted condylar osteogenesis in middle‐aged mice, thereby allowing the mandible to achieve a stable protruding position. In addition, DFM enhanced the volume and quality of MA‐induced condylar new bone formation. Furthermore, histological analysis revealed that DFM enhanced MA‐induced condylar subchondral ossification. Mechanistically, it was confirmed that DFM increased the number of H‐type vessels and their coupled Osterix + osteoprogenitors by upregulating the hypoxia‐inducible factor (HIF)‐1α signalling pathway, thereby enhancing MA‐induced condylar osteogenesis. Conclusion Applying DFM to enhance MA‐induced condylar osteogenesis through H‐type angiogenesis is expected to be an effective strategy to achieve favourable functional orthopaedic treatment effectiveness in non‐growing patients.