背景:损伤组织的再生依赖于干/祖细胞,它可以经历增殖和成熟过程以取代丢失的细胞和细胞外基质(ECM)。骨骼比其他组织具有更高的再生能力,骨髓中有丰富的间充质祖细胞,骨膜,和周围的肌肉。然而,骨折的治疗并不总是成功的;大量的临床病例报告描述了由于各种原因导致的骨不连或延迟愈合。通过干细胞疗法补充外源性干细胞有望改善治疗结果;然而,有几个缺点,包括需要特殊的设备来扩增体外的干细胞,移植后体内细胞存活率低,和肿瘤并发症。使用内源性干/祖细胞,而不是外源性细胞,将是一个可能的解决方案,但目前尚不清楚这些细胞是如何向损伤部位迁移的。
方法:弹性蛋白微原纤维界面定位蛋白2(Emilin2)的趋化能力,由巨噬细胞产生,通过迁移测定和LC-MS/MS鉴定。使用Emilin2-/-小鼠进一步研究了Emilin2在骨再生中的功能。
结果:结果表明,在响应骨损伤时,ECM蛋白Emilin2增加。由巨噬细胞产生,Emilin2对间充质细胞表现出趋化特性。Emilin2-/-小鼠经历了延迟的骨再生,损伤后间充质细胞减少。局部施用重组Emilin2蛋白增强骨再生。
结论:Emilin2通过增加间充质细胞在骨再生中起关键作用。因此,Emilin2可通过募集内源性祖细胞来治疗骨折。
BACKGROUND: Regeneration of injured tissue is dependent on stem/progenitor cells, which can undergo proliferation and maturation processes to replace the lost cells and extracellular matrix (ECM). Bone has a higher regenerative capacity than other tissues, with abundant mesenchymal progenitor cells in the bone marrow, periosteum, and surrounding muscle. However, the treatment of bone fractures is not always successful; a marked number of clinical case reports have described nonunion or delayed healing for various reasons. Supplementation of exogenous stem cells by stem cell therapy is anticipated to improve treatment outcomes; however, there are several drawbacks including the need for special devices for the expansion of stem cells outside the body, low rate of cell viability in the body after transplantation, and oncological complications. The use of endogenous stem/progenitor cells, instead of exogenous cells, would be a possible solution, but it is unclear how these cells migrate towards the injury site.
METHODS: The chemoattractant capacity of the elastin microfibril interface located protein 2 (Emilin2), generated by macrophages, was identified by the migration assay and LC-MS/MS. The functions of Emilin2 in bone regeneration were further studied using Emilin2-/- mice.
RESULTS: The results show that in response to bone injury, there was an increase in Emilin2, an ECM protein. Produced by macrophages, Emilin2 exhibited chemoattractant properties towards mesenchymal cells. Emilin2-/- mice underwent delayed bone regeneration, with a decrease in mesenchymal cells after injury. Local administration of recombinant Emilin2 protein enhanced bone regeneration.
CONCLUSIONS: Emilin2 plays a crucial role in bone regeneration by increasing mesenchymal cells. Therefore, Emilin2 can be used for the treatment of bone fracture by recruiting endogenous progenitor cells.