Mesenchymal stem cell-derived apoptotic bodies alleviate alveolar bone destruction by regulating osteoclast differentiation and function

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International Journal of Oral Science Pub Date : 2023-12-01 DOI:10.1038/s41368-023-00255-y
Xiaoyan Li, Yiyang Jiang, Xu Liu, Jingfei Fu, Juan Du, Zhenhua Luo, Junji Xu, Ujjal Kumar Bhawal, Yi Liu, Lijia Guo
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Abstract

Periodontitis is caused by overactive osteoclast activity that results in the loss of periodontal supporting tissue and mesenchymal stem cells (MSCs) are essential for periodontal regeneration. However, the hypoxic periodontal microenvironment during periodontitis induces the apoptosis of MSCs. Apoptotic bodies (ABs) are the major product of apoptotic cells and have been attracting increased attention as potential mediators for periodontitis treatment, thus we investigated the effects of ABs derived from MSCs on periodontitis. MSCs were derived from bone marrows of mice and were cultured under hypoxic conditions for 72 h, after which ABs were isolated from the culture supernatant using a multi-filtration system. The results demonstrate that ABs derived from MSCs inhibited osteoclast differentiation and alveolar bone resorption. miRNA array analysis showed that miR-223-3p is highly enriched in those ABs and is critical for their therapeutic effects. Targetscan and luciferase activity results confirmed that Itgb1 is targeted by miR-223-3p, which interferes with the function of osteoclasts. Additionally, DC-STAMP is a key regulator that mediates membrane infusion. ABs and pre-osteoclasts expressed high levels of DC-STAMP on their membranes, which mediates the engulfment of ABs by pre-osteoclasts. ABs with knock-down of DC-STAMP failed to be engulfed by pre-osteoclasts. Collectively, MSC-derived ABs are targeted to be engulfed by pre-osteoclasts via DC-STAMP, which rescued alveolar bone loss by transferring miR-223-3p to osteoclasts, which in turn led to the attenuation of their differentiation and bone resorption. These results suggest that MSC-derived ABs are promising therapeutic agents for the treatment of periodontitis.

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间充质干细胞衍生的凋亡小体通过调节破骨细胞分化和功能减轻牙槽骨破坏
牙周炎是由过度活跃的破骨细胞活动引起的,导致牙周支持组织和间充质干细胞(MSCs)的损失,这对牙周再生至关重要。然而,在牙周炎期间,低氧的牙周微环境诱导MSCs凋亡。凋亡小体(apoptosis bodies, ABs)是凋亡细胞的主要产物,作为牙周炎治疗的潜在介质而受到越来越多的关注,因此我们研究了来自MSCs的ABs对牙周炎的作用。从小鼠骨髓中提取间充质干细胞,在缺氧条件下培养72小时,然后用多层过滤系统从培养上清中分离抗体。结果表明,MSCs来源的抗体抑制破骨细胞分化和牙槽骨吸收。miRNA阵列分析显示,miR-223-3p在这些抗体中高度富集,对其治疗效果至关重要。Targetscan和荧光素酶活性结果证实,Itgb1被miR-223-3p靶向,从而干扰破骨细胞的功能。此外,DC-STAMP是介导膜灌注的关键调节因子。抗体和破骨前细胞在其膜上表达高水平的DC-STAMP,这介导了破骨前细胞对抗体的吞噬。DC-STAMP敲低的抗体不能被破骨前细胞吞噬。总的来说,msc衍生的抗体通过DC-STAMP被破骨前细胞吞噬,通过将miR-223-3p转移到破骨细胞中来挽救牙槽骨丢失,从而导致其分化和骨吸收的衰减。这些结果表明,msc来源的抗体是治疗牙周炎的有希望的治疗药物。
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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
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