Abstract:The ability of Biosilicate® with two crystalline phases (BioS-2P) to drive osteoblast differentiation encourages the investigation of the cellular mechanisms involved in this process. Then, the aim of our study was to analyze the large-scale gene expression of osteoblasts grown on BioS-2P compared with Bioglass 45S5 (45S5). Osteoblasts differentiated from rat bone marrow mesenchymal stem cells were cultured under osteogenic conditions on BioS-2P, 45S5 and polystyrene (control). After 10 days, the expression of… Show more
“…The metabonegenic mechanism may be worthy of future study to explore whether nutrient-or energysensing pathways (e.g., the mTOR and the AMPK pathways) are involved in citrate metabonegenic regulation, especially since citrate uptake increased mTOR-dependent protein synthesis and diminished the hypothalamic AMPK activity following exogenous supplementation (40). Moreover, the involvement and upregulation of SLC13a5 rather than SLC16a1 as the lactate membrane transporter during active bone formation (10,11,41) highlights the advantages of citrate-based materials for orthopedic applications compared with traditional PLA-based materials.…”
A comprehensive understanding of the key microenvironmental signals regulating bone regeneration is pivotal for the effective design of bioinspired orthopedic materials. Here, we identified citrate as an osteopromotive factor and revealed its metabonegenic role in mediating citrate metabolism and its downstream effects on the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Our studies show that extracellular citrate uptake through solute carrier family 13, member 5 (SLC13a5) supports osteogenic differentiation via regulation of energy-producing metabolic pathways, leading to elevated cell energy status that fuels the high metabolic demands of hMSC osteodifferentiation. We next identified citrate and phosphoserine (PSer) as a synergistic pair in polymeric design, exhibiting concerted action not only in metabonegenic potential for orthopedic regeneration but also in facile reactivity in a fluorescent system for materials tracking and imaging. We designed a citrate/phosphoserine-based photoluminescent biodegradable polymer (BPLP-PSer), which was fabricated into BPLP-PSer/hydroxyapatite composite microparticulate scaffolds that demonstrated significant improvements in bone regeneration and tissue response in rat femoral-condyle and cranial-defect models. We believe that the present study may inspire the development of new generations of biomimetic biomaterials that better recapitulate the metabolic microenvironments of stem cells to meet the dynamic needs of cellular growth, differentiation, and maturation for use in tissue engineering.
“…The metabonegenic mechanism may be worthy of future study to explore whether nutrient-or energysensing pathways (e.g., the mTOR and the AMPK pathways) are involved in citrate metabonegenic regulation, especially since citrate uptake increased mTOR-dependent protein synthesis and diminished the hypothalamic AMPK activity following exogenous supplementation (40). Moreover, the involvement and upregulation of SLC13a5 rather than SLC16a1 as the lactate membrane transporter during active bone formation (10,11,41) highlights the advantages of citrate-based materials for orthopedic applications compared with traditional PLA-based materials.…”
A comprehensive understanding of the key microenvironmental signals regulating bone regeneration is pivotal for the effective design of bioinspired orthopedic materials. Here, we identified citrate as an osteopromotive factor and revealed its metabonegenic role in mediating citrate metabolism and its downstream effects on the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Our studies show that extracellular citrate uptake through solute carrier family 13, member 5 (SLC13a5) supports osteogenic differentiation via regulation of energy-producing metabolic pathways, leading to elevated cell energy status that fuels the high metabolic demands of hMSC osteodifferentiation. We next identified citrate and phosphoserine (PSer) as a synergistic pair in polymeric design, exhibiting concerted action not only in metabonegenic potential for orthopedic regeneration but also in facile reactivity in a fluorescent system for materials tracking and imaging. We designed a citrate/phosphoserine-based photoluminescent biodegradable polymer (BPLP-PSer), which was fabricated into BPLP-PSer/hydroxyapatite composite microparticulate scaffolds that demonstrated significant improvements in bone regeneration and tissue response in rat femoral-condyle and cranial-defect models. We believe that the present study may inspire the development of new generations of biomimetic biomaterials that better recapitulate the metabolic microenvironments of stem cells to meet the dynamic needs of cellular growth, differentiation, and maturation for use in tissue engineering.
“…43,44 The osteoblastic differentiation has been characterized by the gene expression of bone markers, alkaline phosphatase activity, and deposition of mineralized matrix. [43][44][45] Regarding the origin, the clustering of samples showed that MSCs from both sources present similar gene expression profiles, but differences in the expression of genes directly related to the processes of osteoblast differentiation and osteogenesis, such as Ibsp, Alpl, and Dlx5, suggest that BM-MSCs are more committed to osteoblast differentiation, which positively affects the osteogenic potential of these cells. For instance, the overexpression of Dlx5 inhibits adipocyte differentiation while inducing osteoblast differentiation of MSCs.…”
Mesenchymal stem cells (MSCs) have been used in therapies for bone tissue healing. The aim of this study was to investigate the effect of cell source and osteoblast differentiation on gene expression profiles of MSCs from bone marrow (BM-MSCs) or adipose tissue (AT-MSCs) to contribute for selecting a suitable cell population to be used in cell-based strategies for bone regeneration. BM-MSCs and AT-MSCs were cultured in growth medium to keep MSCs characteristics or in osteogenic medium to induce osteoblast differentiation (BM-OBs and AT-OBs). The transcriptomic analysis was performed by microarray covering the entire rat functional genome. It was observed that cells from bone marrow presented higher expression of genes related to osteogenesis, whereas cells from adipose tissue showed a higher expression of genes related to angiogenesis and adipocyte differentiation, irrespective of cell differentiation. By comparing cells from the same source, MSCs from both sources exhibited higher expression of genes involved in angiogenesis, osteoblast differentiation, and bone morphogenesis than osteoblasts. The clustering analysis showed that AT-OBs exhibited a gene expression profile closer to MSCs from both sources than BM-OBs, suggesting that BM-OBs were in a more advanced stage of differentiation. In conclusion, our results suggest that in cell-based therapies for bone regeneration AT-MSCs could be considered for angiogenic purposes, whereas BM-MSCs and osteoblasts differentiated from either source could be better for osteogenic approaches.
“…In fact, the growth of an apatite‐like layer may provide an ideal environment for osteoblast colonization, proliferation, and differentiation (Jell & Stevens, ; Zhao et al, ). Moreover, BG extracts deeply impact the gene expression of osteoblasts, and this effect may be, at least in part, associated with their osteostimulation ability (de Godoy et al, ; Ferraz et al, ; Xynos et al, ). The up‐regulation of genes previously recognized as participating in the mineralization process (e.g., Bglap, Dmp1, Rcor2, and Phospho1) indicates a more advanced stage of osteoblast differentiation when these cells are cultured in contact with BGs (Ferraz et al, ).…”
Section: Discussionmentioning
confidence: 99%
“…Therefore, chemical signals delivered from BGs, mainly ionic products, have been widely reported to promote matrix synthesis of fibroblasts and angiogenic differentiation of endothelial cells (Gorustovich, Roether, & Boccaccini, 2010;Shih, Lu, Hsieh, Chen, & Chen, 2014). The calcium phosphate layer spontaneously produced after BG contact with body fluids can form a chemical bond with bone and dissolve over time, provoking bone cell activity through the up-regulation of several genes in osteoblasts (Ferraz et al, 2017;Hoppe et al, 2011;Xynos, Edgar, Buttery, Hench, & Polak, 2001). All these characteristics have made them attractive to many applications in tissue engineering, particularly in orthopaedic and dentistry fields (Habraken, Habibovic, Epple, & Bohner, 2016).…”
Bioactive glass has been proved to have many applications in bioengineering due to its bone regenerative properties. In this work, an innovative, highly resorbable bioactive glass containing 90% SiO2 (BG90) to be used as a bone substitute was developed. The BG90 was synthetized by the sol–gel process with the dry step at room temperature. The biomaterial showed in vitro and in vivo bioactivities even with silica content up to 90%. Moreover, the BG90 presented high porosity and surface area due to its homogenously interconnected porous network. In vitro, it was observed to have high cell viability and marked osteoblastic differentiation of rat bone marrow‐derived cells when in contact with BG90 ion extracts. The BG90 transplantation into rat tibia defects was analysed at 1, 2, 3, 4, 7, and 10 weeks post‐operatively and compared with the defects of negative (no graft) and positive (autogenous bone graft) controls. After 4 weeks of grafting, the BG90 was totally resorbed and induced higher bone formation than did the positive control. Bone morphogenetic protein 2 (BMP‐2) expression at the grafting site peaked at 1 week and decreased similarly after 7 weeks for all groups. Only the BG90 group was still exhibiting BMP‐2 expression in the last experimental time. Our data demonstrated that the BG90 could be an attractive candidate to provide useful approaches in hard‐tissue bioengineering.
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