Local administration of a hedgehog agonist accelerates fracture healing in a mouse model
Local administration of a hedgehog agonist accelerates fracture healing in a mouse model
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DOI：
10.1016/j.bbrc.2016.09.134
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发表时间：
2016-10-28
影响因子：
3.1
通讯作者：
Ohba, Shinsuke
中科院分区：
文献类型：
--
作者：
Kashiwagi, Miki;Hojo, Hironori;Ohba, Shinsuke
骨折愈合过程经历多个生物学阶段，包括从软骨骨痂到骨痂形成的过渡。Hedgehog（Hh）信号通路是参与这些过程的最强有力的信号通路之一，但小分子化合物激活Hh信号通路对修复过程的影响尚未得到解决。在这里，我们研究了局部和一次性注射Hh激动剂（称为平滑激动剂（SAG））对小鼠模型骨折愈合的治疗效果。三维显微计算机断层扫描的定量分析表明，在手术后14天，SAG给药增加了软骨性骨痂和骨性骨痂的大小。组织学分析表明，SAG给药增加了软骨愈伤组织中表达增殖标志物和软骨细胞标志物的细胞数量以及骨痂中表达成骨细胞标志物的细胞数量。这些结果表明，SAG施用导致骨折愈合期间愈伤组织形成的增强，这至少部分地由软骨愈伤组织中软骨细胞增殖的增加和骨性愈伤组织中骨形成的促进介导。因此，使用SAG介导的方案的治疗策略可用于治疗骨折。(C)2016 Elsevier Inc. All rights reserved.
Bone fracture healing is processed through multiple biological stages including the transition from cartilaginous callus to bony callus formation. Because of its specific, temporal and indispensable functions demonstrated by mouse genetic studies, Hedgehog (Hh) signaling is one of the most potent signaling pathways involved in these processes, but the effect of Hh-signaling activation by small compounds on the repair process had not yet been addressed. Here we examined therapeutic effects of local and one shot-administration of the Hh agonist known as smoothened agonist (SAG) on bone fracture healing in a mouse model. A quantitative analysis with three-dimensional micro-computed tomography showed that SAG administration increased the size of both the cartilaginous callus and bony callus at 14 days after the surgery. A histological analysis showed that SAG administration increased the number of cells expressing a proliferation marker and a chondrocyte marker in cartilaginous callus as well as the cells expressing an osteoblast marker in bony callus. These results indicate that the SAG administration resulted in an enhancement of callus formation during bone fracture healing, which is at least in part mediated by an increase in chondrocyte proliferation in cartilaginous callus and the promotion of bone formation in bony callus. Therapeutic strategies with a SAG-mediated protocol may thus be useful for the treatment of bone fractures. (C) 2016 Elsevier Inc. All rights reserved.