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Recombinant human bone morphogenetic protein‐9 potently induces osteogenic differentiation of human periodontal ligament fibroblasts
Author(s) -
Fuchigami Sawako,
Nakamura Toshiaki,
Furue Kirara,
Sena Kotaro,
Shinohara Yukiya,
Noguchi Kazuyuki
Publication year - 2016
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/eos.12249
Subject(s) - chemistry , bone morphogenetic protein , periodontal fiber , bone morphogenetic protein 2 , osteopontin , runx2 , microbiology and biotechnology , bone sialoprotein , bone morphogenetic protein 7 , small interfering rna , alkaline phosphatase , osteoblast , chordin , bone morphogenetic protein 6 , bone morphogenetic protein 5 , noggin , transfection , endocrinology , biology , in vitro , osteocalcin , biochemistry , dentistry , medicine , gene , enzyme
To accomplish effective periodontal regeneration for periodontal defects, several regenerative methods using growth and differentiation factors, including bone morphogenetic proteins ( BMP s), have been developed. Bone morphogenetic protein‐9 exhibits the most potent osteogenic activity of this growth factor family. However, it is unclear whether exogenous BMP ‐9 can induce osteogenic differentiation in human periodontal ligament ( PDL ) fibroblasts. Here, we examined the effects of recombinant human (rh) BMP ‐9 on osteoblastic differentiation in human PDL fibroblasts in vitro, compared with rh BMP ‐2. Recombinant human BMP ‐9 potently induced alkaline phosphatase ( ALP ) activity, mineralization, and increased expression of runt‐related transcription factor‐ 2 /core binding factor alpha 1 (RUNX2/CBFA1) , osterix, inhibitor of DNA binding/differentiation‐1 ( ID 1 ), osteopontin, and bone sialoprotein genes, compared with rh BMP ‐2. The levels of rh BMP ‐9‐induced osterix and ALP mRNA were significantly reduced in activin receptor‐like kinase‐1 and ‐2 small interfering RNA (si RNA )‐transfected human PDL fibroblasts. Recombinant human BMP ‐9‐induced ALP activity was not inhibited by noggin, in contrast to rh BMP ‐2 induced ALP activity, which was. Phosphorylation of SMAD 1/5/8 in human PDL fibroblasts was induced by addition of rh BMP ‐9. Recombinant human BMP ‐9‐induced ALP activity was suppressed by SB 203580, SP 600125, and U0126, which are inhibitors of p38, c‐Jun N‐terminal kinase ( JNK ), and extracellular signal‐regulated kinase 1/2 ( ERK 1/2), respectively. Our data suggest that rh BMP ‐9 is a potent inducer of the differentiation of human PDL fibroblasts into osteoblast‐like cells and that this may be mediated by the SMAD and mitogen‐activated protein kinase (p38, ERK 1/2, and JNK ) pathways.