MicroRNA-146a-loaded magnesium silicate nanospheres promote bone regeneration in an inflammatory microenvironment.

IF 14.3 1区 医学 Q1 CELL & TISSUE ENGINEERING
Jiakang Yang, Jing Shuai, Lixuen Siow, Jingyi Lu, Miao Sun, Wenyue An, Mengfei Yu, Baixiang Wang, Qianming Chen
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Abstract

Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge, as chronic local inflammation can largely impair bone healing. Here, we used magnesium silicate nanospheres (MSNs) to load microRNA-146a-5p (miR-146a) to fabricate a nanobiomaterial, MSN+miR-146a, which showed synergistic promoting effects on the osteogenic differentiation of human dental pulp stem cells (hDPSCs). In addition, miR-146a exhibited an anti-inflammatory effect on mouse bone marrow-derived macrophages (BMMs) under lipopolysaccharide (LPS) stimulation by inhibiting the NF-κB pathway via targeting tumor necrosis factor receptor-associated factor 6 (TRAF6), and MSNs could simultaneously promote M2 polarization of BMMs. MiR-146a was also found to inhibit osteoclast formation. Finally, the dual osteogenic-promoting and immunoregulatory effects of MSN+miR-146a were further validated in a stimulated infected mouse mandibular bone defect model via delivery by a photocuring hydrogel. Collectively, the MSN+miR-146a complex revealed good potential in treating inflammatory irregular oral-maxillofacial bone defects.

Abstract Image

微RNA-146a负载硅酸镁纳米球促进炎症微环境中的骨再生
在炎症微环境下重建不规则的口腔颌面骨缺损仍是一项挑战,因为慢性局部炎症会在很大程度上影响骨愈合。在这里,我们利用硅酸镁纳米球(MSNs)负载microRNA-146a-5p(miR-146a)来制造一种纳米生物材料MSN+miR-146a,它对人牙髓干细胞(hDPSCs)的成骨分化具有协同促进作用。此外,在脂多糖(LPS)刺激下,miR-146a通过靶向肿瘤坏死因子受体相关因子6(TRAF6)抑制NF-κB通路,对小鼠骨髓源性巨噬细胞(BMMs)具有抗炎作用,MSNs还能同时促进BMMs的M2极化。研究还发现 MiR-146a 可抑制破骨细胞的形成。最后,MSN+miR-146a的双重成骨促进和免疫调节作用在通过光固化水凝胶递送的受刺激感染小鼠下颌骨缺损模型中得到了进一步验证。总之,MSN+miR-146a 复合物在治疗炎症性不规则口腔颌面骨缺损方面具有良好的潜力。
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来源期刊
Bone Research
Bone Research CELL & TISSUE ENGINEERING-
CiteScore
20.00
自引率
4.70%
发文量
289
审稿时长
20 weeks
期刊介绍: Established in 2013, Bone Research is a newly-founded English-language periodical that centers on the basic and clinical facets of bone biology, pathophysiology, and regeneration. It is dedicated to championing key findings emerging from both basic investigations and clinical research concerning bone-related topics. The journal's objective is to globally disseminate research in bone-related physiology, pathology, diseases, and treatment, contributing to the advancement of knowledge in this field.
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