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Zoledronate interrupts pre-osteoclast-induced angiogenesis via SDF-1/CXCR4 pathway

Mohamed Awad1, Elizabeth Taylor-Diaz2, Amany Tawfik3

  • 1Dental College of Georgia, Augusta University, Augusta, GA, USA.

Bone Reports
|November 25, 2024
PubMed
Abstract

Insights

Pre-osteoclast signaling via the SDF-1/CXCR4 pathway is crucial for post-traumatic angiogenesis in alveolar bone. Disrupting this pathway with zoledronate hinders healing and may contribute to medication-related osteonecrosis of the jaw (MRONJ).

Area of Science:

  • Oral and Maxillofacial Surgery
  • Bone Biology
  • Angiogenesis Research

Background:

  • Pre-osteoclasts are implicated in alveolar bone healing after dental trauma.
  • The SDF-1/CXCR4 pathway is a potential mediator of this process.
  • Medication-related osteonecrosis of the jaw (MRONJ) involves impaired bone healing.

Purpose of the Study:

  • To investigate the role of pre-osteoclast signaling in post-traumatic alveolar bone angiogenesis.
  • To determine the effect of zoledronate (Zol) on the SDF-1/CXCR4 pathway and subsequent angiogenesis.
  • To explore the potential link between Zol-induced disruption and MRONJ pathogenesis.

Main Methods:

  • In vitro assessment of zoledronate's effect on SDF-1 expression in pre-osteoclasts.
  • In vitro evaluation of conditioned media from zoledronate-treated pre-osteoclasts on HUVEC behavior (differentiation, migration, tube formation, CXCR4 expression).
  • In vivo quantification of zoledronate's impact on post-traumatic alveolar bone vascularization in rats using microCT-angiography and immunohistochemistry.

Main Results:

  • Zoledronate significantly reduced SDF-1 expression in pre-osteoclasts and CXCR4 expression/activity in HUVECs.
  • Zoledronate inhibited HUVEC migration and tube formation, effects reversible by SDF-1.
  • In vivo, zoledronate treatment led to reduced CD31+ HUVECs, blood vessel volume, and vessel number in rat alveolar bone.

Conclusions:

  • Pre-osteoclasts are essential for initiating angiogenesis in alveolar bone post-trauma.
  • Disruption of the SDF-1/CXCR4 pathway by zoledronate impairs this angiogenic response.
  • This impairment may represent a key factor in the development of MRONJ.
Keywords:
AngiogenesisCXCR4OsteoclastsOsteonecrosisSDF1Zoledronate

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