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

J Oral Rehabil. 2023 Mar;50(3):234-242. doi: 10.1111/joor.13410. Epub 2023 Jan 16.

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.

Keywords: H-type vessels; angiogenesis; deferoxamine mesylate; mandibular advancement; mandibular condyle; osteogenesis.

MeSH terms

  • Animals
  • Deferoxamine / pharmacology
  • Male
  • Mandibular Advancement*
  • Mandibular Condyle* / diagnostic imaging
  • Mandibular Condyle* / pathology
  • Mice
  • Mice, Inbred C57BL
  • Osteogenesis / physiology
  • X-Ray Microtomography

Substances

  • Deferoxamine