Osteocytic connexin 43 channels affect fracture healing
Osteocytic connexin 43 channels affect fracture healing
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骨细胞连接蛋白 43 通道影响骨折愈合
DOI：
10.1002/jcp.28581
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Xu, Huiyun
中科院分区：
文献类型：
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作者：
Chen, Yunhe;Chen, Meng;Xu, Huiyun
细胞之间的相互作用对于有序地向前推进骨折愈合非常关键。连接蛋白43形成的缝隙连接和半通道介导相邻细胞之间以及细胞与细胞外环境之间的通讯。成骨细胞/骨细胞中Cx43的缺失导致骨折愈合延迟。为了研究骨细胞中两个通道在骨修复中的作用，产生了两种具有由10 kb-DMP 1启动子驱动的Cx43显性阴性突变体的转基因小鼠模型：R76 W（间隙连接被阻断，而半通道被促进）和Delta 130-136（间隙连接和半通道都被阻断）。R76 W小鼠（促进半通道）显示新骨形成显著增加，而在Delta 130-136中观察到破骨细胞生成和愈合延迟（间隙连接受损），但在R76 W小鼠中未观察到（促进半通道可能恢复延迟）。这些结果表明，缝隙连接和半通道在骨修复中发挥着相似的作用。
The cross-talk between cells is very critical for moving forward fracture healing in an orderly manner. Connexin (Cx) 43-formed gap junctions and hemichannels mediate the communication between adjacent cells and cells and extracellular environment. Loss of Cx43 in osteoblasts/osteocytes results in delayed fracture healing. For investigating the role of two channels in osteocytes in bone repair, two transgenic mouse models with Cx43 dominant negative mutants driven by a 10kb-DMP1 promoter were generated: R76W (gap junctions are blocked, whereas hemichannels are promoted) and Delta 130-136 (both gap junctions and hemichannels are blocked). R76W mice (promotion of hemichannels) showed a significant increase of new bone formation, whereasdelayed osteoclastogenesis and healing was observed in Delta 130-136 (impairment of gap junctions), but not in R76W mice (hemichannel promotion may recover the delay). These results suggest that gap junctions and hemichannels play some similar and cooperative roles in bone repair.