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

Abstract

The effect of functional orthopedic 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 much worthy of studying. To investigate whether deferoxamine mesylate (DFM) enhances MA-induced condylar osteogenesis in middle-aged mice. 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. 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 up-regulating the hypoxia-inducible factor (HIF)-1α signaling pathway, thereby enhancing MA-induced condylar osteogenesis. Applying DFM to enhance MA-induced condylar osteogenesis through H-type angiogenesis is expected to be an effective strategy to achieve favorable functional orthopedic treatment effectiveness in non-growing patients.