title: Effects of recombinant dentin sialoprotein in dental pulp cells.
abstract: Dentin sialophosphoprotein (DSPP) is critical for dentin mineralization. However, the function of dentin sialoprotein (DSP), the cleaved product of DSPP, remains unclear. This study aimed to investigate the signal transduction pathways and effects of recombinant human DSP (rh-DSP) on proliferation, migration, and odontoblastic differentiation in human dental pulp cells (HDPCs). The exogenous addition of rh-DSP enhanced the proliferation and migration of HDPCs in dose- and time-dependent manners. rh-DSP markedly increased ALP activity, calcium nodule formation, and levels of odontoblastic marker mRNA. rh-DSP increased BMP-2 expression and Smad1/5/8 phosphorylation, which was blocked by the BMP antagonist, noggin. Furthermore, rh-DSP phosphorylated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), Akt, and IκB-α, and induced the nuclear translocation of the NF-κB p65 subunit. Analysis of these data demonstrates a novel signaling function of rh-DSP for the promotion of growth, migration, and differentiation in HDPCS via the BMP/Smad, JNK, ERK, MAPK, and NF-κB signaling pathways, suggesting that rh-DSP may have therapeutic utility in dentin regeneration or dental pulp tissue engineering.
authors.affiliation: Department of Maxillofacial Tissue Regeneration, School of Dentistry and Institute of Oral Biology, Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Lee
authors.forename: S-Y
authors.initials: SY
authors.lastname: Kim
authors.forename: S-H
authors.initials: SH
authors.lastname: Park
authors.forename: J-J
authors.initials: JJ
authors.lastname: Kim
authors.forename: J-H
authors.initials: JH
authors.lastname: Jang
authors.forename: E-C
authors.initials: EC
authors.lastname: Kim
mesh_terms: D000469:Alkaline Phosphatase / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000187:drug effects; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009804:Odontoblasts / Q000187:drug effects; D051058:Oncogene Protein v-akt / Q000187:drug effects; D010750:Phosphoproteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects; D011994:Recombinant Proteins; D012795:Sialoglycoproteins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051898:Smad1 Protein / Q000187:drug effects; D051902:Smad5 Protein / Q000187:drug effects; D051904:Smad8 Protein / Q000187:drug effects; D013997:Time Factors; D014074:Tooth Calcification / Q000187:drug effects; D051996:Transcription Factor RelA / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000187:drug effects; D000099176:Noggin Protein; D000099311:Dentin Sialophosphoprotein
chemical_list: D000469:Alkaline Phosphatase; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D020672:I-kappa B Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D051058:Oncogene Protein v-akt; D010750:Phosphoproteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D051898:Smad1 Protein; D051902:Smad5 Protein; D051904:Smad8 Protein; D051996:Transcription Factor RelA; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; D000099311:Dentin Sialophosphoprotein; C525718:BMP2 protein, human; C000606204:NFKBIA protein, human; C497399:SMAD1 protein, human; C497797:SMAD5 protein, human; C107514:SMAD9 protein, human