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含锰生物陶瓷通过清除活性氧抑制破骨细胞生成并促进骨质疏松性骨再生。

Mn-containing bioceramics inhibit osteoclastogenesis and promote osteoporotic bone regeneration via scavenging ROS.

作者信息

Li Jianmei, Deng Cuijun, Liang Wanyuan, Kang Fei, Bai Yun, Ma Bing, Wu Chengtie, Dong Shiwu

机构信息

Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University (Army Medical University), Chongqing, 400038, China.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China.

出版信息

Bioact Mater. 2021 Apr 12;6(11):3839-3850. doi: 10.1016/j.bioactmat.2021.03.039. eCollection 2021 Nov.

Abstract

Osteoporosis is caused by an osteoclast activation mechanism. People suffering from osteoporosis are prone to bone defects. Increasing evidence indicates that scavenging reactive oxygen species (ROS) can inhibit receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis and suppress ovariectomy-induced osteoporosis. It is critical to develop biomaterials with antioxidant properties to modulate osteoclast activity for treating osteoporotic bone defects. Previous studies have shown that manganese (Mn) can improve bone regeneration, and Mn supplementation may treat osteoporosis. However, the effect of Mn on osteoclasts and the role of Mn in osteoporotic bone defects remain unclear. In present research, a model bioceramic, Mn-contained β-tricalcium phosphate (Mn-TCP) was prepared by introducing Mn into β-TCP. The introduction of Mn into β-TCP significantly improved the scavenging of oxygen radicals and nitrogen radicals, demonstrating that Mn-TCP bioceramics might have antioxidant properties. The and findings revealed that Mn ions released from Mn-TCP bioceramics could distinctly inhibit the formation and function of osteoclasts, promote the differentiation of osteoblasts, and accelerate bone regeneration under osteoporotic conditions . Mechanistically, Mn-TCP bioceramics inhibited osteoclastogenesis and promoted the regeneration of osteoporotic bone defects by scavenging ROS via Nrf2 activation. These results suggest that Mn-containing bioceramics with osteoconductivity, ROS scavenging and bone resorption inhibition abilities may be an ideal biomaterial for the treatment of osteoporotic bone defect.

摘要

骨质疏松症是由破骨细胞激活机制引起的。患有骨质疏松症的人容易出现骨缺损。越来越多的证据表明,清除活性氧(ROS)可以抑制核因子κB受体激活剂配体(RANKL)诱导的破骨细胞生成,并抑制卵巢切除诱导的骨质疏松症。开发具有抗氧化性能的生物材料以调节破骨细胞活性来治疗骨质疏松性骨缺损至关重要。先前的研究表明,锰(Mn)可以促进骨再生,补充锰可能治疗骨质疏松症。然而,锰对破骨细胞的影响以及锰在骨质疏松性骨缺损中的作用仍不清楚。在本研究中,通过将锰引入β-磷酸三钙(β-TCP)制备了一种模型生物陶瓷,含锰β-磷酸三钙(Mn-TCP)。将锰引入β-TCP显著提高了对氧自由基和氮自由基的清除能力,表明Mn-TCP生物陶瓷可能具有抗氧化性能。[此处原文缺失部分内容]的研究结果表明,从Mn-TCP生物陶瓷释放的锰离子可以明显抑制破骨细胞的形成和功能,促进成骨细胞的分化,并在骨质疏松条件下加速骨再生。从机制上讲,Mn-TCP生物陶瓷通过激活Nrf2清除ROS来抑制破骨细胞生成并促进骨质疏松性骨缺损的再生。这些结果表明,具有骨传导性、ROS清除和骨吸收抑制能力的含锰生物陶瓷可能是治疗骨质疏松性骨缺损的理想生物材料。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2a4/8050801/53a8c8ce26d8/ga1.jpg

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