title: Bone Morphogenetic Protein-9 Enhances Osteogenic Differentiation of Human Periodontal Ligament Stem Cells via the JNK Pathway.
abstract: 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.
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yanen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Weizhong
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Clinical research center, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Su
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Haochen
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Dalin
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Cao
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D005434:Flow Cytometry; D055427:Growth Differentiation Factor 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D010513:Periodontal Ligament / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D055427:Growth Differentiation Factor 2; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D048031:JNK Mitogen-Activated Protein Kinases