Effects of Recombinant Dentin Sialoprotein in Dental Pulp Cells
Effects of Recombinant Dentin Sialoprotein in Dental Pulp Cells
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DOI：
10.1177/0022034511436113
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发表时间：
2012-04-01
影响因子：
7.6
通讯作者：
Kim, E. -C.
中科院分区：
文献类型：
--
作者：
Lee, S. -Y.;Kim, S. -Y.;Kim, E. -C.
牙本质涎磷蛋白（DSPP）是牙本质矿化的关键。然而，DSPP的裂解产物牙本质涎蛋白（DSP）的功能尚不清楚。本研究旨在探讨重组人DSP（recombinant human DSP，rh-DSP）对人牙髓细胞（human dental pulp cells，HDPCs）增殖、迁移和向成牙本质细胞分化的影响及其信号转导途径。外源性rh-DSP可促进HDPCs的增殖和迁移，并呈剂量和时间依赖性。rh-DSP显著增加ALP活性、钙结节形成和成牙本质细胞标志物mRNA水平。rh-DSP增加BMP-2表达和Smad 1/5/8磷酸化，这被BMP拮抗剂noggin阻断。此外，rh-DSP磷酸化细胞外信号调节激酶（ERK），c-Jun N-末端激酶（JNK），Akt和I κ B-α，并诱导NF-κ B p65亚基的核转位。对这些数据的分析表明，rh-DSP通过BMP/Smad、JNK、ERK、MAPK和NF-κ B信号通路促进HDPCS的生长、迁移和分化的新型信号传导功能，表明rh-DSP可能在牙本质再生或牙髓组织工程中具有治疗效用。
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 I kappa B-alpha, and induced the nuclear translocation of the NF-kappa B 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-kappa B signaling pathways, suggesting that rh-DSP may have therapeutic utility in dentin regeneration or dental pulp tissue engineering.