Enhanced bone regeneration via multimodal actions of synthetic peptide SVVYGLR on osteoprogenitors and osteoclasts
Enhanced bone regeneration via multimodal actions of synthetic peptide SVVYGLR on osteoprogenitors and osteoclasts
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DOI：
10.1016/j.biomaterials.2009.05.032
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发表时间：
2009-09-01
期刊：
影响因子：
14
通讯作者：
Yatani, Hirofumi
中科院分区：
文献类型：
--
作者：
Egusa, Hiroshi;Kaneda, Yoshitoshi;Yatani, Hirofumi
最近，结合序列Ser-Val-Val-Tyr-Gly-Leu-Arg（SVVYGLR）被发现与骨桥蛋白中的RGD序列相邻，表明参与骨免疫串扰。本研究的目的是研究合成的SVVYGLR肽在骨祖细胞和破骨细胞中的生物活性功能，并研究其在骨再生中的潜在应用。SVVYGLR肽显著增强了几种人间充质细胞（包括骨髓来源的间充质干细胞）的粘附和增殖，并且α v β 3整联蛋白参与了细胞与肽的粘附。此外，肽减少RAW264.7细胞和正常鼠前破骨细胞的破骨细胞生成期间TRAP阳性多核细胞的数量，并且还抑制NFAT活性和破骨细胞生成相关mRNA的表达。当用含有肽或PBS（对照）的胶原海绵填充大鼠颅骨中的标准化骨缺损时，3周后肽组中移植部位中TRAP阳性破骨细胞的数量显著较低。到第5周，在肽组中观察到移植胶原海绵的吸收显著增强，并且在海绵内和周围观察到新骨形成。这些数据表明，SVVYGLR是一种有效的骨组织再生的生物活性肽，可促进成骨细胞的附着和增殖，同时还抑制破骨细胞生成。(C)2009爱思唯尔有限公司保留所有权利。
Recently, the binding sequence Ser-Val-Val-Tyr-Gly-Leu-Arg (SVVYGLR) was found adjacent to the RGD sequence in osteopontin, suggesting involvement in osteo-immune cross-talk. The aim of this study was to investigate bioactive functions of a synthetic SVVYGLR peptide in osteoprogenitor cells and osteoclasts, and to examine potential applications in bone regeneration. The SVVYGLR peptide significantly enhanced the adhesion and proliferation of several human mesenchymal cells including bone marrow-derived mesenchymal stem cells, and alpha v beta 3 integrin was involved in cell attachment to the peptide. Additionally, the peptide reduced the number of TRAP-positive multinucleated cells during osteoclastogenesis of RAW264.7 cells and normal murine pre-osteoclasts, and also suppressed NFAT activity and expression of osteoclastogenesis-related mRNAs. When standardized bone defects in rat calvariae were filled with a collagen sponge containing the peptide or PBS (control), the number of TRAP-positive osteoclasts in the grafted sites after 3 weeks was significantly lower in the peptide group. By the 5th week, significantly enhanced resorption of the grafted collagen sponge and new bone formation was observed within and surrounding the sponge in the peptide group. These data suggest that SVVYGLR is an effective bioactive peptide for bone tissue regeneration that promotes attachment and proliferation of osteogenic cells while also suppressing osteoclastogenesis. (C) 2009 Elsevier Ltd. All rights reserved.