Beta-adrenergic receptor antagonist propranolol prevents bisphosphonate-related osteonecrosis of the jaw by promoting osteogenesis

IF 3.1 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Journal of Dental Sciences Pub Date : 2025-01-01 DOI:10.1016/j.jds.2024.04.016
Qianxin Du , Qizhang Wang , Yuhao Wang , Chengzhi Zhao , Jian Pan
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Abstract

Background/purpose

Bisphosphonate-related osteonecrosis of the jaw (BRONJ), a complication arising from the use of bisphosphonates (BPs), inflicts long-term suffering on patients. Currently, there is still a lack of effective treatments. This study aimed to explore the preventive effects of propranolol (PRO) on BRONJ in vitro and in vivo, given PRO's potential in bone health enhancement.

Materials and methods

In vitro, effect of PRO on zoledronic acid (ZA)-pretreated bone marrow mesenchymal stem cells (BMSCs) was detected by cell counting kit-8, alkaline phosphatase (ALP) staining, alizarin red staining, real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. In vivo, forty mice were divided into four groups: control, ZA, PRO, and ZA-PRO. The maxillary extraction sockets sides were analyzed with micro-CT and histomorphometry. Hematoxylin-eosin (H&E), Masson staining, immunofluorescence staining of ALP, bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2) and TUNEL staining were performed.

Results

PRO increased proliferation and osteogenic differentiation of BMSCs. PRO stimulated bone formation and facilitated the healing process in zoledronic acid-induced osteonecrosis of jaw in mouse model. Compared with ZA group, control and PRO group showed more BMP2+, RUNX2+, and ALP+ cells (P < 0.05). However, PRO rescued the decreased expression of ALP, RUNX2, BMP2 due to ZA and decreased the expression of TUNEL (P < 0.05).

Conclusion

The findings suggest that propranolol may offer a promising preventive strategy against BRONJ by enhancing bone regeneration. This research contributes to the understanding of the pathogenesis of BRONJ and opens avenues for potential treatments of BRONJ focusing on β-adrenergic signaling.
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β-肾上腺素能受体拮抗剂普萘洛尔通过促进骨生成预防与双膦酸盐相关的颌骨坏死
背景/目的双膦酸盐相关性颌骨骨坏死(BRONJ)是使用双膦酸盐(bp)引起的并发症,对患者造成长期痛苦。目前,仍缺乏有效的治疗方法。鉴于propranolol (PRO)具有促进骨骼健康的潜力,本研究旨在探讨propranolol (PRO)在体外和体内对BRONJ的预防作用。材料与方法体外采用细胞计数试剂盒-8、碱性磷酸酶(ALP)染色、茜素红染色、实时定量聚合酶链反应(RT-qPCR)和Western blot检测PRO对唑来膦酸(ZA)预处理的骨髓间充质干细胞(BMSCs)的影响。在体内,将40只小鼠分为4组:对照组、ZA组、PRO组和ZA-PRO组。采用显微ct和组织形态学对上颌拔牙槽侧进行分析。进行苏木精-伊红(H&;E)染色、Masson染色、ALP、骨形态发生蛋白2 (BMP2)、矮子相关转录因子2 (RUNX2)免疫荧光染色和TUNEL染色。结果spro能促进骨髓间充质干细胞的增殖和成骨分化。PRO能促进唑来膦酸所致小鼠颌骨坏死骨形成,促进骨愈合。与ZA组比较,对照组和PRO组BMP2+、RUNX2+、ALP+细胞增多(P <;0.05)。然而,PRO挽救了ZA导致的ALP、RUNX2、BMP2的表达下降,并降低了TUNEL的表达(P <;0.05)。结论心得安可能通过促进骨再生来预防BRONJ。这项研究有助于了解BRONJ的发病机制,并为BRONJ的潜在治疗开辟了途径,重点关注β-肾上腺素能信号传导。
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来源期刊
Journal of Dental Sciences
Journal of Dental Sciences 医学-牙科与口腔外科
CiteScore
5.10
自引率
14.30%
发文量
348
审稿时长
6 days
期刊介绍: he Journal of Dental Sciences (JDS), published quarterly, is the official and open access publication of the Association for Dental Sciences of the Republic of China (ADS-ROC). The precedent journal of the JDS is the Chinese Dental Journal (CDJ) which had already been covered by MEDLINE in 1988. As the CDJ continued to prove its importance in the region, the ADS-ROC decided to move to the international community by publishing an English journal. Hence, the birth of the JDS in 2006. The JDS is indexed in the SCI Expanded since 2008. It is also indexed in Scopus, and EMCare, ScienceDirect, SIIC Data Bases. The topics covered by the JDS include all fields of basic and clinical dentistry. Some manuscripts focusing on the study of certain endemic diseases such as dental caries and periodontal diseases in particular regions of any country as well as oral pre-cancers, oral cancers, and oral submucous fibrosis related to betel nut chewing habit are also considered for publication. Besides, the JDS also publishes articles about the efficacy of a new treatment modality on oral verrucous hyperplasia or early oral squamous cell carcinoma.
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