Effect of α2‑macroglobulin in the early stage of jaw osteoradionecrosis

Li,Jie; Yin,Ping; Chen,Xueying; Kong,Xiangbo; Zhong,Wanzhen; Ge,Yaping; She,Yangyang; Xian,Xuehong; Qi,Lei; Lin,Zhi; Moe,Justine; Fang,Silian

doi:10.3892/ijo.2020.5051

Effect of α2‑macroglobulin in the early stage of jaw osteoradionecrosis

Authors:
- Jie Li
- Ping Yin
- Xueying Chen
- Xiangbo Kong
- Wanzhen Zhong
- Yaping Ge
- Yangyang She
- Xuehong Xian
- Lei Qi
- Zhi Lin
- Justine Moe
- Silian Fang
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Affiliations: Department of Oral and Maxillofacial Surgery, The Sixth Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510655, P.R. China, Department of Oral and Maxillofacial Surgery, The Sixth Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510655, P.R. China, Department of Stomatology, Sun Yat‑sen Memorial Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China, Department of Oral and Cranio‑maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai 200001, P.R. China, Department of Oral and Maxillofacial Surgery, University of Michigan, Ann Arbor, MI 48109, USA
Published online on: April 23, 2020 https://doi.org/10.3892/ijo.2020.5051
Pages: 213-222
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Advanced osteoradionecrosis (ORN) is one of the most serious complications in patients with head and neck cancer, resulting in poor prognosis. Numerous studies have therefore focused on the pathogenesis and interventions of ORN early stage. The present study aimed to investigate whether α2‑macroglobulin (α2M) could prevent early‑stage jaw osteoradionecrosis caused by radiotherapy (RT). Following local injection of α2M, a single dose of 30 Gy was delivered to rats for pathological exploration. For 28 days, the irradiated mandible and soft tissues were examined for potential changes. Furthermore, primary human bone marrow mesenchymal stem cells pretreated with α2M followed by 8 Gy irradiation (IR) were also used. Tartrate‑resistant acid phosphatase assay, terminal uridine deoxynucleotidyl nick end labeling assay and immunohistochemical staining were performed on irradiated mandibular bone, tongue or buccal mucosa tissues from rats. Cell proliferation was assessed by evaluating the cell morphology by microscopy and by using the cell counting kit‑8. Fluorescence staining, flow cytometry and western blotting were conducted to detect the reactive oxygen species level, cell apoptosis and protein expression of superoxide dismutase 2 (SOD2), heme oxygenase‑1 (HO‑1) and phosphorylated Akt following irradiation. The results demonstrated that α2M attenuated physical inflammation, osteoclasts number and fat vacuole accumulation in mandibular bone marrow and bone marrow cell apoptosis following IR in vivo. Furthermore, α2M pretreatment suppressed the expression of 8‑hydroxy‑2'‑deoxyguanosine in mandibular bone and tongue paraffin embedded sections, which is a marker of oxidative damage, and increased SOD2 expression in mucosa and tongue paraffin embedded sections. The present study demonstrated the efficient regulation of antioxidative enzymes, including SOD2 and heme oxygenase‑1, and reduction in oxidative damage by α2M. In addition, in vitro results confirmed that α2M may protect cells from apoptosis and suppress reactive oxygen species accumulation. Overall, the present study demonstrated that α2M treatment may exert some radioprotective effects in early‑stage ORN via antioxidant mechanisms, and may therefore be considered as a potential alternative molecule in clinical prophylactic treatments.

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