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

IF 3.4 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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引用次数: 0

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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来源期刊

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.