title: Combined effects of dentin sialoprotein and bone morphogenetic protein-2 on differentiation in human cementoblasts.
abstract: The aim of this study is to determine the effects of the combination of recombinant human BMP-2 (rh-BMP-2) and dentin sialoprotein (rh-DSP) on growth and differentiation in human cementoblasts and determine the underlying signal transduction mechanism. Compared to treatment of cementoblasts with either rh-BMP-2 or rh-DSP alone, the combination of rh-BMP-2 and rh-DSP synergistically increased cell growth, ALP activity, nodule formation and expression of differentiation markers. The differentiation-promoting effect was also observed in periodontal ligament cells and an osteoblastic cell line. Likewise, combination of rh-DSP and rh-BMP-2 increased BMP-2 mRNA expression and Smad1/5/8 phosphorylation, which was blocked by the BMP antagonist noggin. The expression levels of α2β1 integrin and RhoA, as well as the phosphorylation status of FAK and Akt, were increased by the combination of rh-BMP-2 and rh-DSP in a time-dependent manner. In addition, rh-BMP-2 and rh-DSP enhanced expression of Wnt ligands, β-catenin activation and GSK-3β phosphorylation, all of which were inhibited by the Wnt receptor antagonist DKK1. Furthermore, treatment with rh-DSP plus rh-BMP-2 resulted in phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 and also induced the nuclear translocation of the NF-κB p65 subunit, which was blocked by noggin. This study demonstrates for the first time that rh-DSP and rh-BMP-2 act synergistically, enhancing each other's ability to stimulate cementoblastic cell growth and differentiation in vitro via autocrine BMP, integrin, Wnt/β-catenin, MAP kinase and NF-κB pathways. These results support the therapeutic potential of a combination strategy for aiding periodontal regeneration.
authors.affiliation: Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth & Periodontal Regeneration (MRC), Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Lee
authors.forename: Q-Schick
authors.initials: QS
authors.lastname: Auh
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Kang
authors.forename: Hyung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Kwantae
authors.initials: K
authors.lastname: Noh
authors.forename: Jun-Hyeog
authors.initials: JH
authors.lastname: Jang
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003739:Dental Cementum / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D006801:Humans; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010750:Phosphoproteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D000099311:Dentin Sialophosphoprotein
chemical_list: D055396:Bone Morphogenetic Protein 2; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; D000099311:Dentin Sialophosphoprotein; C499469:recombinant human bone morphogenetic protein-2