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

• Published in: PloS one Vol. 12; no. 1; p. e0169123
• Main Authors: Wang, Pei, Wang, Yanen, Tang, Weizhong, Wang, Xingxing, Pang, Yanan, Yang, Su, Wei, Yibo, Gao, Haochen, Wang, Dalin, Cao, Zhizhong
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04.01.2017; Public Library of Science (PLoS)
• Subjects: Adenoviridae; Alkaline phosphatase; Biocompatibility; Biology and Life Sciences; Biomedical materials; Blotting, Western; Bone growth; Bone morphogenetic protein 9; Bone morphogenetic proteins; c-Jun protein; Cbfa-1 protein; Cell Differentiation - genetics; Cell Differentiation - physiology; Cells, Cultured; Crosstalk; Differentiation; Evaluation; Flow Cytometry; Gene expression; Gene therapy; Gene transfer; Growth Differentiation Factor 2 - genetics; Growth Differentiation Factor 2 - metabolism; Growth factors; Health aspects; Human subjects; Humans; Immunogenicity; JNK Mitogen-Activated Protein Kinases - genetics; JNK Mitogen-Activated Protein Kinases - metabolism; JNK protein; Kinases; Ligaments; Medicine and Health Sciences; Mineralization; Orthodontics; Ossification (ectopic); Osteocalcin; Osteogenesis; Osteogenesis - genetics; Osteogenesis - physiology; Osteopontin; Periodontal ligament; Periodontal Ligament - cytology; Phosphorylation; Proteins; Pulmonary arteries; Regeneration; Regeneration (physiology); Research and Analysis Methods; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleic acid; RNA; Signal transduction; siRNA; Smad2 protein; Smad2 Protein - genetics; Smad2 Protein - metabolism; Smad3 Protein - genetics; Smad3 Protein - metabolism; Stem cell transplantation; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Transcription factors; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0169123

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.