Overexpression of HIF-1alpha in Bone Marrow Mesenchymal Stem Cells Promote the Repair of Mandibular Condylar Osteochondral Defect in a Rabbit Model
Overexpression of HIF-1alpha in Bone Marrow Mesenchymal Stem Cells Promote the Repair of Mandibular Condylar Osteochondral Defect in a Rabbit Model
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DOI：
10.1016/j.joms.2020.10.013
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发表时间：
2021-01-29
影响因子：
1.9
通讯作者：
Zhou, Qing
中科院分区：
文献类型：
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作者：
Cheng, Mo-sha;Yi, Xin;Zhou, Qing
目的：颞下颌关节软骨自身修复能力有限。低氧诱导因子-1 α（HIF-1 α）可以诱导干细胞促进软骨修复。本研究旨在系统评价HIF-1 α过表达的骨髓间充质干细胞（BMSCs）复合胶原支架对兔TMJ髁突骨软骨缺损修复的影响。方法：在40只新西兰白色兔右侧髁突建立直径3 mm ×深度2 mm的骨软骨缺损模型。单纯空支架组、胶原支架组、BMSCs/COL组、HIF-1 α过表达BMSCs/COL组。通过大体检查、番红O-固绿色染色（Solarbio，Beijing，China）和免疫组化染色监测髁突软骨的组织形态学特征。用微型计算机断层扫描检查软骨下骨的变化。结果：植入后12周，组织学观察显示单纯空组和COL组骨软骨缺损以纤维组织填充为主，而BMSCs/COL组和HIF 1-α过表达BMSCs/COL组以纤维软骨修复缺损。此外，与BMSCs/COL组相比，HIF-1 α过表达BMSCs/COL组的软骨组织化更好。骨软骨缺损可引起软骨下骨异常增生，移植BMSCs，尤其是HIF-1 α过表达的BMSCs可减轻骨增生。结论：高表达HIF-1 α的BMSCs联合COL支架移植可促进髁突软骨修复，抑制髁突骨软骨下骨硬化。(C)2020年美国口腔颌面外科医师协会
Purpose: The self-repair ability of temporomandibular joint (TMJ) cartilage is limited. Hypoxia-inducible factor-1 alpha (HIF-1alpha) may induce stem cells to promote chondrogenic repair. The purpose of this study was to systematically evaluate the effect of HIF-1alpha overexpression in bone marrow mesenchymal stem cells (BMSCs) combined with collagen scaffolds on the repair of TMJ condylar osteochondral defects in a rabbit model.Methods: Osteochondral defects of 3-mm diameter x 2-mm depth were created at the right side of the mandibular condyle in 40 New Zealand white rabbits. The defect sites were treated with simple empty, collagen scaffolds (COL), BMSCs/COL, and HIF-1alpha overexpression BMSCs/COL groups. The histomorphologic features of condylar cartilage were monitored by gross examination, safranin O-fast green staining (Solarbio, Beijing, China), and immunohistochemical staining. The changes in subchondral bone were examined by microcomputed tomography. Immunofluorescence staining was used to trace the transplanted BMSCs in vivo.Results: At 12 weeks postimplantation, histologic staining showed that the osteochondral defects in the simple empty and COL groups were mainly filled with fibrous tissue, whereas the BMSCs/COL and HIF1-alpha overexpression BMSCs/COL groups repaired the defect with fibrocartilage. Furthermore, the cartilage was better organized in the HIF-1alpha overexpression BMSCs/COL group compared with the BMSCs/COL group. Microcomputed tomography showed that osteochondral defects can cause abnormal hyperosteogeny in subchondral bone, and the transplantation of BMSCs, especially HIF-1alpha overexpression BMSCs, may alleviate osteosclerosis. Immunofluorescence staining showed that HIF-1alpha overexpression can promote the survival of transplanted BMSCs.Conclusions: The transplantation of HIF-1alpha overexpression BMSCs combined with a COL scaffold promotes cartilaginous repair of condylar cartilage and inhibits subchondral bone sclerosis in TMJ condylar osteochondral defect rabbits. (C) 2020 American Association of Oral and Maxillofacial Surgeons