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

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 expose...

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Published inScientific reports Vol. 8; no. 1; p. 9224
Main Authors Bakhit, Alamuddin, Kawashima, Nobuyuki, Hashimoto, Kentaro, Noda, Sonoko, Nara, Keisuke, Kuramoto, Masashi, Tazawa, Kento, Okiji, Takashi
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 15.06.2018
Nature Publishing Group
Subjects
1-Phosphatidylinositol 3-kinase
13
13/106
13/109
13/89
13/95
38/39
38/77
631/136/142
631/136/2091
631/1647/2017/2003
631/80/86/1999
82/80
AKT protein
Alkaline phosphatase
Animals
Bone matrix
Bone sialoprotein
Calcification, Physiologic - drug effects
Calcium-sensing receptors
Cell growth
Cell proliferation
Dental pulp
Dental Pulp - cytology
Dental Pulp - metabolism
Dspp protein
Gene expression
Gene Expression Regulation - drug effects
Humanities and Social Sciences
Kinases
Mice
Mice, Inbred ICR
Mineralization
Molars
multidisciplinary
Nodules
Odontoblasts - cytology
Odontoblasts - metabolism
Odontogenesis - drug effects
Osteoblasts
Osteocalcin
Osteogenesis - drug effects
Osteoporosis
Papillae
Phosphorylation
Rats
Science
Science (multidisciplinary)
siRNA
Strontium
Teeth
Thiophenes - pharmacology
Tissues
Topical application
Online AccessGet full text

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Abstract 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 .
AbstractList 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.
Abstract 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 .
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.
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 .
ArticleNumber 9224
Author Tazawa, Kento
Noda, Sonoko
Kawashima, Nobuyuki
Hashimoto, Kentaro
Bakhit, Alamuddin
Okiji, Takashi
Nara, Keisuke
Kuramoto, Masashi
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/29907831$$D View this record in MEDLINE/PubMed
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Snippet This study examined the effects and mechanisms of strontium ranelate (SrRn)—a drug used to treat osteoporosis—on the proliferation and...
This study examined the effects and mechanisms of strontium ranelate (SrRn)-a drug used to treat osteoporosis-on the proliferation and...
Abstract This study examined the effects and mechanisms of strontium ranelate (SrRn)—a drug used to treat osteoporosis—on the proliferation and...
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SubjectTerms 1-Phosphatidylinositol 3-kinase
13
13/106
13/109
13/89
13/95
38/39
38/77
631/136/142
631/136/2091
631/1647/2017/2003
631/80/86/1999
82/80
AKT protein
Alkaline phosphatase
Animals
Bone matrix
Bone sialoprotein
Calcification, Physiologic - drug effects
Calcium-sensing receptors
Cell growth
Cell proliferation
Dental pulp
Dental Pulp - cytology
Dental Pulp - metabolism
Dspp protein
Gene expression
Gene Expression Regulation - drug effects
Humanities and Social Sciences
Kinases
Mice
Mice, Inbred ICR
Mineralization
Molars
multidisciplinary
Nodules
Odontoblasts - cytology
Odontoblasts - metabolism
Odontogenesis - drug effects
Osteoblasts
Osteocalcin
Osteogenesis - drug effects
Osteoporosis
Papillae
Phosphorylation
Rats
Science
Science (multidisciplinary)
siRNA
Strontium
Teeth
Thiophenes - pharmacology
Tissues
Topical application
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Title Strontium ranelate promotes odonto-/osteogenic differentiation/mineralization of dental papillae cells in vitro and mineralized tissue formation of the dental pulp in vivo
URI https://link.springer.com/article/10.1038/s41598-018-27461-7
https://www.ncbi.nlm.nih.gov/pubmed/29907831
https://www.proquest.com/docview/2055930784
https://pubmed.ncbi.nlm.nih.gov/PMC6003917
Volume 8
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