Chondrocyte-to-osteoblast transformation in mandibular fracture repair.

Chondrocyte-to-osteoblast transformation in mandibular fracture repair.
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DOI:
10.1002/jor.24904
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发表时间:
2021-08
期刊:
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
影响因子:
--
通讯作者:
Bahney CS
Bahney CS
中科院分区:
其他
文献类型:
--
作者:
Wong SA;Hu DP;Slocum J;Lam C;Nguyen M;Miclau T;Marcucio RS;Bahney CS

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大多数骨折研究都是使用长骨骨折模型进行的,对驱动颅面修复的机制的研究明显较少。然而,颅面骨在发育机制和胚胎起源方面都不同于长骨。因此,它们的愈合机制可能不同。在这项研究中,我们利用稳定和不稳定的下颌骨骨折模型,调查的途径调节修复。然而,完全稳定的环钻缺损直接形成骨,在同一解剖位置的横向骨折内的机械运动促进了骨重建之前的稳健软骨形成。研究长骨骨折的文献表明,软骨细胞是软骨内修复过程中成骨细胞的直接前体。用Aggrecan-CreERT 2::Ai 9 tdTomato小鼠进行谱系追踪证明,下颌骨骨痂软骨细胞也直接有助于新骨的形成。此外,免疫组织化学显示,位于软骨-骨交界处的软骨细胞表达Sox 2,这表明这些软骨细胞的可塑性可能有助于这种软骨细胞向成骨细胞的转化。基于软骨细胞在骨修复中的直接作用,我们测试了软骨移植物在愈合临界尺寸下颌骨缺损中的有效性。虽然空缺损保持未桥接并填充纤维组织,但软骨植入产生骨桥接和稳健的骨髓腔形成,表明新形成的骨的健康血管化。移植软骨直接促进新骨形成,因为新形成的骨的很大一部分是移植物/供体衍生的。总之,这些数据证明了软骨细胞向成骨细胞转化在下颌骨软骨内修复过程中的重要作用,以及使用软骨作为组织移植物治愈颅面缺损的治疗前景。
The majority of fracture research has been conducted using long bone fracture models, with significantly less research into the mechanisms driving craniofacial repair. However, craniofacial bones differ from long bones in both their developmental mechanism and embryonic origin. Thus, it is possible that their healing mechanisms could differ. In this study we utilize stabilized and unstabilized mandible fracture models to investigate the pathways regulating repair. Whereas fully stable trephine defects in the ramus form bone directly, mechanical motion within a transverse fracture across the same anatomical location promoted robust cartilage formation before boney remodeling. Literature investigating long bone fractures show chondrocytes are a direct precursor of osteoblasts during endochondral repair. Lineage tracing with Aggrecan‐CreERT2::Ai9 tdTomato mice demonstrated that mandibular callus chondrocytes also directly contribute to the formation of new bone. Furthermore, immunohistochemistry revealed that chondrocytes located at the chondro‐osseous junction expressed Sox2, suggesting that plasticity of these chondrocytes may facilitate this chondrocyte‐to‐osteoblast transformation. Based on the direct role chondrocytes play in bone repair, we tested the efficacy of cartilage grafts in healing critical‐sized mandibular defects. Whereas empty defects remained unbridged and filled with fibrous tissue, cartilage engraftment produced bony‐bridging and robust marrow cavity formation, indicating healthy vascularization of the newly formed bone. Engrafted cartilage directly contributed to new bone formation since a significant portion of the newly formed bone was graft/donor‐derived. Taken together these data demonstrate the important role of chondrocyte‐to‐osteoblast transformation during mandibular endochondral repair and the therapeutic promise of using cartilage as a tissue graft to heal craniofacial defects.
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