Mineral trioxide aggregate solution inhibits osteoclast differentiation through the maintenance of osteoprotegerin expression in osteoblasts
Division of Molecular Signaling and Biochemistry, Department of Biosciences, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan. Journal of Biomedical Materials Research Part A
(Impact Factor: 3.37).
02/2011; 96(2):358-64. DOI: 10.1002/jbm.a.32990
Mineral trioxide aggregate (MTA) is a therapeutic, endodontic repair material that is reported to exhibit calcified tissue-conductive activity. The aim of this study was to investigate whether MTA may prevent osteoclast differentiation in vitro. MTA solution, but not other commonly used retrofilling materials, such as Dycal, Super-EBA, or intermediate restorative material (IRM) solution, dose-dependently inhibited osteoclastogenesis in cocultures of mouse bone marrow cells (BMCs) with primary osteoblast cells (POBs) induced by 1α,25-dihydroxyvitamin D(3) [1α,25(OH)(2) D(3) ]. Exogenous CaCl(2) medium supplementation did not inhibit osteoclastogenesis in cocultures. Furthermore, MTA solution did not affect receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis, suggesting that POBs are targets of MTA. MTA solution suppressed the 1α,25(OH)(2) D(3) -induced reduction of osteoprotegerin (OPG) mRNA and protein production without changing RANKL expression in POBs. Consistent with this result, MTA solution did not inhibit osteoclastogenesis in cocultures of BMCs and POBs from OPG-deficient mice. Therefore, the maintenance of OPG expression in POBs appears to be critical for the inhibitory effect of MTA solution on osteoclast differentiation.
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Available from: Lucia Forte
- "Osteoblast and osteoclast lineages are fundamental for bone turnover and angiogenetic processes play also a crucial role, as the formation of new capillaries supports osteogenesis during bone remodeling . Cell crosstalk, through direct and indirect intercellular signaling, modifies the expression of cell phenotype when compared to the relative mono-culture, as reported for co-cultures of osteoblast and osteoclast[28,394041. Osteoblast–endothelial cells and osteoclast–endothelial cells co-cultures have also been studied42434445. "
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ABSTRACT: Statement of significance:
The pharmacological activities of the flavonoid quercetin include anti-oxidant and antiinflammatory properties, as well as capability to prevent bone loss. In this paper, we demonstrate that it is possible to synthesize hydroxyapatite functionalized with different amounts of quercetin and obtain new composite materials which display both the good bioactivity of the inorganic phase and the therapeutic properties of the flavonoid. The innovative in vitro model developed in this study, which involves co-culture of osteoblast, osteoclast and endothelial cells, allows to state that the new materials exert a beneficial action onto bone repair microenvironment, stimulating osteoblast proliferation and activity, downregulating osteoclastogenesis, and supporting microangiogenetic processes necessary for new bone formation.
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ABSTRACT: Mineral trioxide aggregate (MTA), a commonly used endodontic repair material, is useful for both basic and clinical research, and the effect of MTA on osteoblast differentiation has been well-defined. However, the effects of MTA on osteoclastic bone resorption are not fully understood. Hence, the aim of this study is to examine the effect of MTA solution in the regulation of osteoclast bone-resorbing activity using osteoclasts formed in co-cultures of primary osteoblasts and bone marrow cells. MTA solution dose-dependently reduced the total area of pits formed by osteoclasts. The reduction of resorption induced by 20% MTA treatment was due to inhibition of osteoclastic bone-resorbing activity and had no effect on osteoclast number. A 20% MTA solution disrupted actin ring formation, a marker of osteoclastic bone resorption, by reducing phosphorylation and kinase activity of c-Src, and mRNA expressions of cathepsin K and mmp-9. A high concentration of MTA solution (50%) induced apoptosis of osteoclasts by increasing the expression of Bim, a member of the BH3-only (Bcl-2 homology) family of pro-apoptotic proteins. Taken together, our results suggest that MTA is a useful retrofilling material for several clinical situations because it both stimulates osteoblast differentiation and inhibits bone resorption.
Available from: Maria Giovanna Gandolfi
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ABSTRACT: The in vitro apatite-forming ability of experimental calcium-silicate hydraulic cements designed for dentistry was investigated.Two cements containing di- and tricalcium-silicate (wTC and wTC-TCP, i.e. wTC added with alpha-TCP) were soaked in different phosphate-containing solutions, namely Dulbecco's Phosphate Buffered Saline (DPBS) or Hank's Balanced Salt Solution (HBSS), at 37°C and investigated over time (from 24h to 6months) by SEM/EDX, micro-Raman and ATR-FTIR.The early formation (24h) of an aragonite/calcite layer onto both cements in both media was observed. Calcium phosphate deposits precipitated within 1–3days in DPBS; spherical particles (spherulites) of apatite appeared after 3–7days. wTC-TCP cement showed earlier, thicker and more homogeneous calcium phosphate deposits than wTC.In HBSS calcite deposits were mainly noticed, while phosphate bands appeared only after 7days; the presence of globular deposits after 14–28days was mostly detected on wTC-TCP.After 6months, an approx. 900micron carbonated apatite layer formed in DPBS whilst a 150–350micron thick calcite/apatite layer generated in HBSS. Also in HBSS the carbonated apatite coating was earlier and thicker on wTC-TCP than wTC.Calcium-silicate cements showed the formation of a bone-like apatite layer, depending on the medium composition and ageing time. The addition of alpha-TCP increases the apatite-forming ability of calcium-silicate cements.Calcium-silicate hydraulic cements doped with alfa-TCP represent attractive materials to improve apical bone healing.
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