Mineral Trioxide Aggregate Inhibits Osteoclastic Bone Resorption

Hashiguchi, Daisuke; Fukushima, Hidefumi; Yasuda, Hisataka; Masuda, Wataru; Tomikawa, Munehiro; Morikawa, Kazumasa; Maki, Kenshi; Jimi, Eijiro

doi:10.1177/0022034511407335

Cited by 34 publications

(24 citation statements)

References 24 publications

(34 reference statements)

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“…Ample reports are available that examined the effects of Ca- and Si-containing biomaterials in promoting or suppressing the differentiation of osteoblast or osteoclast precursors. These materials include Si-substituted apatite [28,29], bioactive glasses [12,30] and calcium silicate cements [31,32]. While all of these materials were found to stimulate differentiation of osteoblast precursors and bone formation, their effects on osteoclastogenesis and cell-mediated bone degradation were ambiguous and appeared to be material-dependent.…”

Section: Discussionmentioning

confidence: 99%

Biphasic silica/apatite co-mineralized collagen scaffolds stimulate osteogenesis and inhibit RANKL-mediated osteoclastogenesis

Jiao

Niu

et al. 2015

Acta Biomaterialia

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The effects of a biphasic mineralized collagen scaffold (BCS) containing intrafibrillar silica and apatite on osteogenesis of mouse mesenchymal stem cells (mMSCs) and inhibition of receptor activator of nuclear factor κB ligand (RANKL)-mediated osteoclastogenesis were investigated in the present study. mMSCs were cultured by exposing to BCS for 7 days for cell proliferation/viability examination, and stimulated to differentiate in osteogenic medium for 7–21 days for evaluation of alkaline phosphatase activity, secretion of osteogenic deposits and expression of osteoblast lineage-specific phenotypic markers. The effect of BCS-conditioned mMSCs on osteoclastogenesis of RAW 264.7 cells was evaluated by tartrate-resistant acid phosphatase staining and resorption pit analysis. The contributions of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K) signal transduction pathways to osteogenesis of mMSCs and their osteoprotegerin (OPG) and RANKL expressions were also evaluated. Compared with unmineralized, intrafibrillarly-silicified or intrafibrillarly-calcified collagen scaffolds, BCS enhanced osteogenic differentiation of mMSCs by activation of the extracellular signal regulated kinases (ERK)/MAPK and p38/MAPK signaling pathways. After mMSCs were exposed to BCS, they up-regulated OPG expression and down-regulated RANKL expression through activation of the p38/MAPK and PI3K/ protein kinase B (Akt) pathways, resulting in inhibition of the differentiation of RAW 264.7 cells into multinucleated osteoclasts and reduction in osteoclast function. These observations collectively suggest that BCS has the potential to be used in bone tissue engineering when the demand for anabolic activities is higher than catabolic metabolism during the initial stage of wound rehabilitation.

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Section: Discussionmentioning

confidence: 99%

Biphasic silica/apatite co-mineralized collagen scaffolds stimulate osteogenesis and inhibit RANKL-mediated osteoclastogenesis

Jiao

Niu

et al. 2015

Acta Biomaterialia

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“…TRAP-positive multinuclear cells [TRAP(ϩ)], containing more than three nuclei, were regarded as osteoclasts. Bone resorption assay using a dentine slice and F-actin ring staining were performed according to the method described (31).…”

Section: Methodsmentioning

confidence: 99%

Involvement of PRIP, Phospholipase C-related, but Catalytically Inactive Protein, in Bone Formation

Tsutsumi

Matsuda

Kotani

et al. 2011

Journal of Biological Chemistry

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PRIP (phospholipase C-related, but catalytically inactive protein) is a novel protein isolated in this laboratory. PRIP-deficient mice showed increased serum gonadotropins, but decreased gonadal steroid hormones. This imbalance was similar to that for the cause of bone disease, such as osteoporosis. In the present study, therefore, we analyzed mutant mice with special reference to the bone property. We first performed three-dimensional analysis of the femur of female mice. The bone mineral density and trabecular bone volume were higher in mutant mice. We further performed histomorphometrical assay of bone formation parameters: bone formation rate, mineral apposition rate, osteoid thickness, and osteoblast number were up-regulated in the mutant, indicating that increased bone mass is caused by the enhancement of bone formation ability. We then cultured primary cells isolated from calvaria prepared from both genotypes. In mutant mice, osteoblast differentiation, as assessed by alkaline phosphatase activity and the expression of osteoblast differentiation marker genes, was enhanced. Moreover, we analyzed the phosphorylation of Smad1/5/8 in response to bone morphogenetic protein, with longer phosphorylation in the mutant. These results indicate that PRIP is implicated in the negative regulation of bone formation.Phospholipase C-related, but catalytically inactive protein (PRIP) 4 was first identified as a novel D-myo-inositol-1,4,5-trisphosphate-binding protein and tentatively named p130 based on molecular size (1). Subsequent molecular cloning studies revealed that the molecule is similar to phospholipase C-␦1 but is catalytically inactive, which is the reason for its revised name, and is expressed predominantly in the brain (2-5). Later, an isoform with relatively broad tissue distribution, including the brain, was reported (6, 7), indicating that PRIP is composed of types 1 and 2. PRIP has a number of binding partners, including GABARAP (␥-aminobutyric acid type A (GABA A ) receptorassociated protein) (8), protein phosphatase-1␣ (9 -11) and -2A (12), and GABA A receptor ␤ subunits (12-14), besides Ins(1,4,5)P 3 (1-5). The finding of these binding partners led us to examine the possible involvement of PRIP in Ins(1,4,5)P 3 -mediated Ca 2ϩ signaling (15, 16) and GABA A receptor signaling (17-20), using cloned culture cells reconstituted with the gene of interest or the gene-silencing technique, and PRIP-1 alone and/or PRIP-1 and -2 gene-deficient mice were also analyzed for GABA A receptor signaling from multiple aspects, including isolated neuron cultures, electrophysiological analysis of brain slices, and behavioral analysis. So far, it is known that there is no great difference between types 1 and 2 regarding the capability of binding to partners described above, therefore, we have mainly used PRIP-1 and -2 gene-deficient mice for further analysis, but not single gene-deficient mice.During the course of mutant animal maintenance, we noticed that mutant couples exhibited decreased litter events and litter size, i...

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“…Hashiguchi et al (2011) investigated that MTA inhibits bone resorption. Taken together, we concluded that MTA in endodontic treatment may affect alveolar bone healing in the resorbed region caused by pulpal infection.…”

Section: Discussionmentioning

confidence: 99%

Mineral trioxide aggregate induces osteoblastogenesis via Atf6

et al. 2015

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Mineral trioxide aggregate (MTA) has been recommended for various uses in endodontics. To understand the effects of MTA on alveolar bone, we examined whether MTA induces osteoblastic differentiation using MC3T3-E1 cells. MTA enhanced mineralization concomitant with alkaline phosphatase activity in a dose- and time-dependent manner. MTA increased production of collagens (Type I and Type III) and matrix metalloproteinases (MMP-9 and MMP-13), suggesting that MTA affects bone matrix remodeling. MTA also induced Bglap (osteocalcin) but not Bmp2 (bone morphogenetic protein-2) mRNA expression. We observed induction of Atf6 (activating transcription factor 6, an endoplasmic reticulum (ER) stress response transcription factor) mRNA expression and activation of Atf6 by MTA treatment. Forced expression of p50Atf6 (active form of Atf6) markedly enhanced Bglap mRNA expression. Chromatin immunoprecipitation assay was performed to investigate the increase in p50Atf6 binding to the Bglap promoter region by MTA treatment. Furthermore, knockdown of Atf6 gene expression by introduction of Tet-on Atf6 shRNA expression vector abrogated MTA-induced mineralization. These results suggest that MTA induces in vitro osteoblastogenesis through the Atf6–osteocalcin axis as ER stress signaling. Therefore, MTA in endodontic treatment may affect alveolar bone healing in the resorbed region caused by pulpal infection.

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Mineral Trioxide Aggregate Inhibits Osteoclastic Bone Resorption

Cited by 34 publications

References 24 publications

Biphasic silica/apatite co-mineralized collagen scaffolds stimulate osteogenesis and inhibit RANKL-mediated osteoclastogenesis

Biphasic silica/apatite co-mineralized collagen scaffolds stimulate osteogenesis and inhibit RANKL-mediated osteoclastogenesis

Involvement of PRIP, Phospholipase C-related, but Catalytically Inactive Protein, in Bone Formation

Mineral trioxide aggregate induces osteoblastogenesis via Atf6

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