Research Paper Volume 12, Issue 20 pp 20743—20752
Determination of the molecular mechanism by which macrophages and γδ-T cells contribute to ZOL-induced ONJ
- 1 Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People’s Hospital, College of Stomatology, Shanghai Jiaotong University, School of Medicine, Shanghai, 200011, China
- 2 Department of Orthopedics, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200336, China
Received: June 11, 2020 Accepted: August 14, 2020 Published: October 25, 2020
https://doi.org/10.18632/aging.104006How to Cite
Copyright: © 2020 Qu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objective: This study aims to explore the molecular mechanism of macrophages and γδ-T cells in the ZOL drug-induced osteonecrosis of jaws based on the IFN-γ involved osteoblast differentiation signaling pathway.
Results: The number and apoptotic rate of CD11b+Gr1hi cells and γδ-T cells in the ONJ group were significantly higher. The TNF-α, IL-1β, IFN-γ, CCL3, CCL4, IL-12 and IL-13 levels were significantly higher in the ONJ group. The expression of CTSK and FGFR3 was lower in the ONJ group, but was higher in the NF-κB and ERBB2IP group.
Conclusion: The proliferation of macrophages and γδ-T cells promote the inflammation in ZOL-induced jaw necrosis.
Methods: A total of 20 patients with osteonecrosis of the jaw from January 2016 to March 2018 were collected and assigned into the observation group, while 20 healthy subjects were assigned into the control group. Furthermore, 40 SD rats were selected and assigned into observation group, while 10 non-treatment SD rats were selected and assigned as controls. The distribution and proportion of CD11b+Gr1hi cells and γδ-T cells in the necrotic tissues of the jaw were analyzed. Then, the TNF-α, IL-1β, IFN-γ, CCL3, CCL4, IL-12 and IL-13 levels were measured. Afterwards, the expression of CTSK, FGFR3, NF-κB and ERBB2IP in the necrotic tissues of the jaw in the animal models were analyzed.
Abbreviations
ONJ: Observation group; NC: Control group; IHC: Immunohistochemical method; MRONJ: Drug-related osteonecrosis of the jaw; BPs: Bisphosphonates; ZOL: Zoledronic acid; IFN-γ: Interferon-γ; FGFR3: Fibroblast growth factor receptor 3; FGFRs: Fibroblast Growth Factor; SD: Sprague Dawley; SPF: Specific Pathogen Free.