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Sci Rep ; 8(1): 7269, 2018 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-29740080

RESUMO

Interleukin 17 (IL-17) stimulates the osteogenic differentiation of progenitor cells in vitro through a synergy with bone morphogenetic protein (BMP)-2. This study investigates whether the diverse responses mediated by IL-17 in vivo also lead to enhanced BMP-2-induced bone formation. Since IL-17 is known to induce osteoclastogenesis, we studied the interactions between IL-17 and BMP-2 in ceramic scaffolds either or not carrying a coating with the bisphosphonate zoledronic acid (ZOL). Histological evaluation revealed that IL-17 alone did not induce any osteoclasts at day 10. On the other hand, BMP-2 clearly stimulated early tissue ingrowth and osteoclastogenesis. Both of these processes were blocked in presence of ZOL. IL-17 signaling restored early vascularized connective tissue formation and osteoclastogenesis induced by BMP-2 in ZOL-coated scaffolds. After 12 weeks, the bone volume induced by co-delivery of BMP-2 and IL-17 was doubled as compared to that induced by BMP-2 alone. We conclude that IL-17 has osteo-stimulatory effects through a synergy with bone-inductive BMP-2. Although local and single application of IL-17 does not mediate osteoclast formation, it could promote other processes involved in bone formation such as connective tissue ingrowth. The use of IL-17 may contribute to the development of improved bone graft substitutes.


Assuntos
Desenvolvimento Ósseo/efeitos dos fármacos , Proteína Morfogenética Óssea 2/genética , Interleucina-17/química , Ácido Zoledrônico/administração & dosagem , Animais , Desenvolvimento Ósseo/genética , Transplante Ósseo/métodos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Cromatografia Líquida de Alta Pressão , Humanos , Interleucina-17/genética , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Coelhos , Células-Tronco/efeitos dos fármacos
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