Mohamed Awad , Elizabeth Taylor-Diaz , Amany Tawfik , Khaled Hussein , Ahmed Elmansi , Mahmoud Elashiry , Ranya Elsayed , Linah Shahoumi , James Borke , William Hill , Fanglong Dong , Mohammed E. Elsalanty
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Then, we tested the effect of pre-osteoclast conditioned medium on HUVEC cell differentiation, migration, tube-formation, and CXCR4 expression and activity in-vitro. Lastly, we quantified the effect of zoledronate treatment on post-traumatic vascular perfusion of alveolar bone, using microCT-angiography and immunohistochemistry.</div></div><div><h3>Results</h3><div>SDF-1 mRNA expression decreased in Zol-treated POCs (<em>p</em> = 0.02). Flow-Cytometry analysis showed a decrease in CXCL-12<sup>+</sup> (SDF-1α) expressing POCs with Zol treatment (<em>p</em> = 0.0058). On the other hand, CXCR4 mRNA expression was significantly inhibited in Zol-treated HUVECs (<em>p</em> = 0.0063). CXCR4 protein expression and activity showed a corresponding dose-dependent downregulation HUVEC surface treated with conditioned media from POC treated with Zol (<em>p</em> = 0.008 and 0.03, respectively). Similar inhibition was observed of HUVEC migration (<em>p</em> = 0.0012), and tube formation (<em>p</em> < 0.0001), effects that were reversed with SDF-1. Finally, there was a significant reduction of CD31<sup>+</sup> HUVECs in Alveolar bone of Zol-treated rats (<em>p</em> = 0.0071), confirmed by significantly lower percentage of blood vessel volume (<em>p</em> = 0.026), and marginally lower vessel number (<em>p</em> = 0.062) in the alveolar bone.</div></div><div><h3>Conclusion</h3><div>Pre-osteoclasts play a crucial role in the initial angiogenic response in alveolar bone following dental extraction. Disruption of this process may be a predisposing factor to osteonecrosis.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"23 ","pages":"Article 101812"},"PeriodicalIF":2.1000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Zoledronate interrupts pre-osteoclast-induced angiogenesis via SDF-1/CXCR4 pathway\",\"authors\":\"Mohamed Awad , Elizabeth Taylor-Diaz , Amany Tawfik , Khaled Hussein , Ahmed Elmansi , Mahmoud Elashiry , Ranya Elsayed , Linah Shahoumi , James Borke , William Hill , Fanglong Dong , Mohammed E. Elsalanty\",\"doi\":\"10.1016/j.bonr.2024.101812\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><div>In this study, we tested the hypothesis that pre-osteoclast signaling is key in triggering post-traumatic angiogenesis in alveolar bone via the SDF-1/CXCR4 pathway. Interruption of osteoclast differentiation through zoledronate (Zol) disrupts the crosstalk between pre-osteoclasts and endothelial cells, hindering the initial angiogenic reaction following dental trauma. This disruption could therefore play a role in the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ).</div></div><div><h3>Methods</h3><div>The effect of zoledronate on the expression of SDF1 was tested in pre-osteoclasts (POC) in vitro. Then, we tested the effect of pre-osteoclast conditioned medium on HUVEC cell differentiation, migration, tube-formation, and CXCR4 expression and activity in-vitro. Lastly, we quantified the effect of zoledronate treatment on post-traumatic vascular perfusion of alveolar bone, using microCT-angiography and immunohistochemistry.</div></div><div><h3>Results</h3><div>SDF-1 mRNA expression decreased in Zol-treated POCs (<em>p</em> = 0.02). Flow-Cytometry analysis showed a decrease in CXCL-12<sup>+</sup> (SDF-1α) expressing POCs with Zol treatment (<em>p</em> = 0.0058). On the other hand, CXCR4 mRNA expression was significantly inhibited in Zol-treated HUVECs (<em>p</em> = 0.0063). CXCR4 protein expression and activity showed a corresponding dose-dependent downregulation HUVEC surface treated with conditioned media from POC treated with Zol (<em>p</em> = 0.008 and 0.03, respectively). Similar inhibition was observed of HUVEC migration (<em>p</em> = 0.0012), and tube formation (<em>p</em> < 0.0001), effects that were reversed with SDF-1. Finally, there was a significant reduction of CD31<sup>+</sup> HUVECs in Alveolar bone of Zol-treated rats (<em>p</em> = 0.0071), confirmed by significantly lower percentage of blood vessel volume (<em>p</em> = 0.026), and marginally lower vessel number (<em>p</em> = 0.062) in the alveolar bone.</div></div><div><h3>Conclusion</h3><div>Pre-osteoclasts play a crucial role in the initial angiogenic response in alveolar bone following dental extraction. 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Zoledronate interrupts pre-osteoclast-induced angiogenesis via SDF-1/CXCR4 pathway
Introduction
In this study, we tested the hypothesis that pre-osteoclast signaling is key in triggering post-traumatic angiogenesis in alveolar bone via the SDF-1/CXCR4 pathway. Interruption of osteoclast differentiation through zoledronate (Zol) disrupts the crosstalk between pre-osteoclasts and endothelial cells, hindering the initial angiogenic reaction following dental trauma. This disruption could therefore play a role in the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ).
Methods
The effect of zoledronate on the expression of SDF1 was tested in pre-osteoclasts (POC) in vitro. Then, we tested the effect of pre-osteoclast conditioned medium on HUVEC cell differentiation, migration, tube-formation, and CXCR4 expression and activity in-vitro. Lastly, we quantified the effect of zoledronate treatment on post-traumatic vascular perfusion of alveolar bone, using microCT-angiography and immunohistochemistry.
Results
SDF-1 mRNA expression decreased in Zol-treated POCs (p = 0.02). Flow-Cytometry analysis showed a decrease in CXCL-12+ (SDF-1α) expressing POCs with Zol treatment (p = 0.0058). On the other hand, CXCR4 mRNA expression was significantly inhibited in Zol-treated HUVECs (p = 0.0063). CXCR4 protein expression and activity showed a corresponding dose-dependent downregulation HUVEC surface treated with conditioned media from POC treated with Zol (p = 0.008 and 0.03, respectively). Similar inhibition was observed of HUVEC migration (p = 0.0012), and tube formation (p < 0.0001), effects that were reversed with SDF-1. Finally, there was a significant reduction of CD31+ HUVECs in Alveolar bone of Zol-treated rats (p = 0.0071), confirmed by significantly lower percentage of blood vessel volume (p = 0.026), and marginally lower vessel number (p = 0.062) in the alveolar bone.
Conclusion
Pre-osteoclasts play a crucial role in the initial angiogenic response in alveolar bone following dental extraction. Disruption of this process may be a predisposing factor to osteonecrosis.
Bone ReportsMedicine-Orthopedics and Sports Medicine
CiteScore
4.30
自引率
4.00%
发文量
444
审稿时长
57 days
期刊介绍：
Bone Reports is an interdisciplinary forum for the rapid publication of Original Research Articles and Case Reports across basic, translational and clinical aspects of bone and mineral metabolism. The journal publishes papers that are scientifically sound, with the peer review process focused principally on verifying sound methodologies, and correct data analysis and interpretation. We welcome studies either replicating or failing to replicate a previous study, and null findings. We fulfil a critical and current need to enhance research by publishing reproducibility studies and null findings.
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