Bone Morphogenetic Protein-9 Enhances Osteogenic Differentiation of Human Periodontal Ligament Stem Cells via the JNK PathwayReportar como inadecuado




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Bone morphogenetic protein-9 BMP9 shows great osteoinductive potential in bone regeneration. Periodontal ligament stem cells PDLSCs with multi-differentiation capability and low immunogenicity are increasingly used as seed cells for periodontal regenerative therapies. In the present study, we investigated the potent osteogenic activity of BMP9 on human PDLSCs hPDLSCs, in which the c-Jun N-terminal kinase JNK pathway is possibly involved. Our results showed that JNK inhibition by the specific inhibitor SP600125 or adenovirus expressing small interfering RNA siRNA targeting JNK AdR-si-JNK significantly decreased BMP9-induced gene and protein expression of early and late osteogenic markers, such as runt-related transcription factor 2 Runx2, alkaline phosphatase ALP, osteopontin OPN, and osteocalcin OCN, in hPDLSCs. We also confirmed the in-vivo positive effect of JNKs on ectopic bone formation induced by hPDLSCs injected into the musculature of athymic nude mice and BMP9 ex vivo gene delivery. For the cellular mechanism, we found that BMP9 activated the phosphorylation of JNKs and Smad2-3, and that JNKs may engage in cross-talk with the Smad2-3 pathway in BMP9-mediated osteogenesis.



Autor: Pei Wang , Yanen Wang , Weizhong Tang , Xingxing Wang, Yanan Pang, Su Yang, Yibo Wei, Haochen Gao, Dalin Wang , Zhizhong Cao

Fuente: http://plos.srce.hr/



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