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| 2. |
- Cardemil, Carina, et al.
(författare)
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Strontium-doped calcium phosphate and hydroxyapatite granules promote different inflammatory and bone remodelling responses in normal and ovariectomised rats.
- 2013
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Ingår i: PLosOne. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-α (TNF-α), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone.
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| 3. |
- Thorfve, Anna, 1982, et al.
(författare)
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Hydroxyapatite coating affects the Wnt signaling pathway during peri-implant healing in vivo
- 2014
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 10:3, s. 1451-1462
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Tidskriftsartikel (refereegranskat)abstract
- Owing to its bio- and osteoconductivity, hydroxyapatite (HA) is a widely used implant material, but its osteogenic properties are only partly evaluated in vitro and in vivo. The present study focused on bone healing adjacent to HA-coated titanium (Ti) implants, with or without incorporated lithium ions (Li+). Special attention was given to the Wnt signaling pathway. The implants were inserted into rat tibia for 7 or 28days and analyzed ex vivo, mainly by histomorphometry and quantitative real-time polymerase chain reaction. HA-coated implants showed, irrespective of Li+ content, bone-implant contact (BIC) and removal torque significantly higher than those of reference Ti. Further, the expressions of OCN, CTSK, COL1A1, LRP5/6 and WISP1 were significantly higher in implant-adherent cells of HA-coated implants, with or without Li+. Significantly higher β-catenin expression and significantly lower COL2A1 expression were observed in peri-implant bone cells from HA with 14ngcm-2 released Li+. Interestingly, Ti implants showed a significantly larger bone area in the threads than HA with 39ngcm-2 released Li+, but had a lower BIC than any HA-coated implant. This study shows that HA, with or without Li+ is a strong activator of the Wnt signaling pathway, and may to some degree explain its high bone induction capacity.
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| 5. |
- Thorfve, Anna, 1982, et al.
(författare)
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Madindoline A Affects the Osteogenic Potential and the Wnt Signaling
- 2014
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Ingår i: Journal of Bone Marrow Research. - : OMICS Publishing Group. - 2329-8820. ; 2:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Human mesenchymal stem cells (hMSCs) have the potential to differentiate at least into adipocytes, chondrocytes and osteoblasts. The differentiation capacity can be modulated by drugs, or chemical substances that affect diverse mechanisms essential for e.g. bone formation. The aim of this study was to investigate the osteoinductive capacity of the interleukin-6 (IL-6) inhibitor Madindoline A (MadA) and its relation to the bone-inducing Wnt signaling pathways. Methods: After stimulation with MadA of hMSC from 4 donors (aged 13-33 years) in an in vitro culture, alkaline phosphatase (ALP) activity and extracellular matrix (ECM) mineralization of hMSCs were quantified and calcification visualized by von Kossa staining. The expression of bone- and Wnt related markers was further studied at gene and protein levels. In addition, stimulation with the non-canonical Wnt5a ligand was added as a positive control, and the effect of MadA on IL-6 gene expression and STAT3 phosphorylation was evaluated. Results: Stimulation with MadA induced increased ECM mineralization and upregulated the expression of the bone related genes RUNX2, COL1A1 and Osteocalcin, although large donor-to-donor differences were observed. Further, MadA affected both the canonical and non-canonical Wnt signaling pathways and displayed a superior osteoinducing property compared to Wnt5a in some cases. Conclusion: In summary, all donors displayed higher gene expression of IL-6 and reduced STAT3 phosphorylation after MadA stimulation. The present results provide for the first time indications of an in vitro osteoinduction potential of the IL-6 inhibitor MadA.
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| 7. |
- Adolfsson, E., et al.
(författare)
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Evaluation of bone ingrowth in Free Form Fabricated scaffolds
- 2008
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Ingår i: Key Engineering Materials. - 1662-9795.
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Tidskriftsartikel (refereegranskat)abstract
- Colloidal processing was used to cast zirconia and hydroxyapatite materials. The cast materials reached densities around 99% when sintered at 1500°C and 1200°C respectively. By controlling the colloidal process the sintered density of hydroxyapatite was also reduced to around 80% when the same sintering condition was used. The casting process was combined with free form fabrication to prepare designed scaffolds with identical macroporosity. These scaffolds were used to evaluate the early bone tissue response in rabbit femur. After six weeks of implantation the bone area in scaffolds of zirconia and hydroxyapatite were compared. In scaffolds of hydroxyapatite the bone area was roughly three times larger compared to corresponding scaffolds of zirconia. When the scaffolds of hydroxyapatite also contained an open microporosity of around 20% the amount of bone was even more pronounced. The results showed the importance of the material composition and the microstructure on the bone regenerating performance of scaffolds.
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| 9. |
- Almqvist, Sofia, 1980, et al.
(författare)
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Amelogenin is phagocytized and induces changes in integrin configuration, gene expression and proliferation of cultured human dermal fibroblasts
- 2010
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Ingår i: Journal of Materials Science. Materials in Medicine. - : Springer Science and Business Media LLC. - 1573-4838 .- 0957-4530. ; 21:3, s. 947-954
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Tidskriftsartikel (refereegranskat)abstract
- Fibroblasts are central in wound healing by expressing important mediators and producing and remodelling extracellular matrix (ECM) components. This study aimed at elucidating possible mechanisms of action of the ECM protein amelogenin on normal human dermal fibroblasts (NHDF). Amelogenin at 100 and 1000 μg/ml increased binding of NHDF via several integrins, including αvβ3, αvβ5 and α5β1. Further, both surface interaction and cellular uptake of amelogenin by NHDF was observed using scanning and transmission electron microscopy. Gene microarray studies showed >8-fold up or down-regulation of genes, of which most are involved in cellular growth, migration and differentiation. The effect of amelogenin was exemplified by increased proliferation over 7 days. In conclusion, the beneficial effects of amelogenin on wound healing are possibly conducted by stimulating fibroblast signalling, proliferation and migration via integrin interactions. It is hypothesized that amelogenin stimulates wound healing by providing connective tissue cells with a temporary extracellular matrix.
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| 10. |
- Almqvist, Sofia, 1980, et al.
(författare)
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Amelogenins modulate cytokine expression in LPS-challenged cultured human macrophages.
- 2012
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Ingår i: Cytokine. - : Elsevier BV. - 1096-0023 .- 1043-4666. ; 58:2, s. 274-9
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Tidskriftsartikel (refereegranskat)abstract
- Amelogenins are enamel matrix proteins with a proven ability to restore tissues in patients with advanced periodontitis and chronic skin wounds. To explore the mechanisms of action of amelogenins in wound inflammation, the in vitro effect on the expression of selected cell mediators involved in inflammation and tissue repair from human monocyte-derived macrophages was studied. Macrophages were treated with amelogenins in serum-enriched medium with simultaneous lipopolysaccharide (LPS) stimulation, for 6, 24 and 72 h, and the conditioned culture medium was analysed for 28 different cytokines. Amelogenin treatment directed the LPS-induced release of both pro- and anti-inflammatory cytokines towards an alternatively activated macrophage phenotype. This change in activation was also demonstrated by the amelogenin-induced secretion of alternative macrophage activation-associated CC chemokine-1 (AMAC-1, also known as CCL18; p<0.001), a well-documented marker of alternative activation. Amelogenins were also shown significantly to increase the macrophage expression of vascular endothelial growth factor and, to a lesser but significant extent, insulin-like growth factor-1 after 24h of culture. The results of the present in vitro study show that monocyte-derived macrophages stimulated by inflammatory agonist LPS respond to the treatment with amelogenins by reducing the pro-inflammatory activity and increasing the expression of tissue repair mediators.
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