Strontium ranelate promotes odonto-/osteogenic differentiation/mineralization of dental papillae cells in vitro and mineralized tissue formation of the dental pulp in vivo

被引:25
作者
Bakhit, Alamuddin [1 ]
Kawashima, Nobuyuki [1 ]
Hashimoto, Kentaro [1 ]
Noda, Sonoko [1 ]
Nara, Keisuke [1 ]
Kuramoto, Masashi [1 ]
Tazawa, Kento [1 ]
Okiji, Takashi [1 ]
机构
[1] TMDU, Grad Sch Med & Dent Sci, Div Oral Hlth Sci, Dept Pulp Biol & Endodont, Tokyo 1138510, Japan
来源
SCIENTIFIC REPORTS | 2018年 / 8卷
基金
日本学术振兴会;
关键词
CALCIUM-SENSING RECEPTOR; TRIOXIDE AGGREGATE; OSTEOBLAST DIFFERENTIATION; ACTIVATION; REPLICATION; HYDROXIDE; DEFECTS; KINASE; CAR; RAT;
D O I
10.1038/s41598-018-27461-7
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
This study examined the effects and mechanisms of strontium ranelate (SrRn)-a drug used to treat osteoporosis-on the proliferation and differentiation/mineralization of cloned dental pulp-like cells (mouse dental papillae cells; MDPs). It also determined whether topical application of SrRn to exposed dental pulp tissue promotes the formation of mineralized tissue in vivo. The MDPs were cultured with or without SrRn, and cell proliferation, odonto-/osteoblastic gene expression, mineralized nodule formation, and Akt phosphorylation were evaluated. The formation of mineralized tissue in SrRn-treated pulp tissue in rat upper first molars was evaluated histologically. The SrRn up-regulated cell proliferation and expression of Alp (alkaline phosphatase), Bsp (bone sialoprotein), Dmp (dentin matrix acidic phosphoprotein)-1, Dspp (dentin sialophosphoprotein), and Oc (osteocalcin) in a dose-dependent manner. Mineralized nodule formation was also enhanced by SrRn. NPS-2143, a calcium-sensing receptor (CaSR) antagonist, and siRNA against the CaSR gene blocked SrRn-induced proliferation, odonto-/osteoblastic gene expression, and mineralized nodule formation. SrRn induced Akt phosphorylation, and this was blocked by NPS-2143. Topical application of SrRn to exposed rat molar pulps induced the formation of osteodentin-like mineralized tissue. Our study revealed for the first time that SrRn promotes proliferation and odonto-/osteogenic differentiation/mineralization of MDPs via PI3K/Akt signaling activated by CaSR in vitro; mineralized tissue forms from the dental pulp in vivo.
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页数:10
相关论文
共 54 条
[1]   Nationwide registry-based analysis of cardiovascular risk factors and adverse outcomes in patients treated with strontium ranelate [J].
Abrahamsen, B. ;
Grove, E. L. ;
Vestergaard, P. .
OSTEOPOROSIS INTERNATIONAL, 2014, 25 (02) :757-762
[2]   Evaluation of mineral trioxide aggregate and calcium hydroxide cement as pulp-capping agents in human teeth [J].
Accorinte, Maria de Lourdes R. ;
Holland, Roberto ;
Reis, Alessandra ;
Bortoluzzi, Marcelo C. ;
Murata, Sueli S. ;
Dezan, Eloy, Jr. ;
Souza, Valdir ;
Alessandro, Loguercio Dourado .
JOURNAL OF ENDODONTICS, 2008, 34 (01) :1-6
[3]   Phosphatidylinositol 3-kinase (PI3K) inhibitors as cancer therapeutics [J].
Akinleye, Akintunde ;
Avvaru, Parthu ;
Furqan, Muhammad ;
Song, Yongping ;
Liu, Delong .
JOURNAL OF HEMATOLOGY & ONCOLOGY, 2013, 6
[4]   Strontium ranelate increases osteoblast activity [J].
Almeida, Monica Marletti ;
Nani, Edson Parra ;
Teixeira, Lucas Novaes ;
Peruzzo, Daiane Cristina ;
Joly, Julio Cesar ;
Napimoga, Marcelo Henrique ;
Martinez, Elizabeth Ferreira .
TISSUE & CELL, 2016, 48 (03) :183-188
[5]   Identification of hard tissue after experimental pulp capping using dentin sialoprotein (DSP) as a marker [J].
Andelin, WE ;
Shabahang, S ;
Wright, K ;
Torabinejad, M .
JOURNAL OF ENDODONTICS, 2003, 29 (10) :646-650
[6]   Toxicity of lithium to humans and the environment - A literature review [J].
Aral, Hal ;
Vecchio-Sadus, Angelica .
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, 2008, 70 (03) :349-356
[7]   The calcium-sensing receptor stimulates JNK in MDCK cells [J].
Arthur, JM ;
Lawrence, MS ;
Payne, CR ;
Rane, MJ ;
McLeish, KR .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 275 (02) :538-541
[8]   Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants [J].
Bain, S. D. ;
Jerome, C. ;
Shen, V. ;
Dupin-Roger, I. ;
Ammann, P. .
OSTEOPOROSIS INTERNATIONAL, 2009, 20 (08) :1417-1428
[9]   Normal matrix mineralization induced by strontium ranelate in MC3T3-E1 osteogenic cells [J].
Barbara, A ;
Delannoy, P ;
Denis, BG ;
Marie, PJ .
METABOLISM-CLINICAL AND EXPERIMENTAL, 2004, 53 (04) :532-537
[10]  
Bergenholtz Gunnar, 2013, Singapore Dent J, V34, P1, DOI 10.1016/j.sdj.2013.11.001