Orthosilicic acid, Si(OH)4, stimulates osteoblast differentiation in vitro by upregulating miR-146a to antagonize NF-kappaB activation.
*microRNA; *NF-kappaB; *Osteoblastic differentiation; *Osteoclastic differentiation; *Silicic acid; Animals; Cell Differentiation/*drug effects; Humans; Mesenchymal Stem Cells/*metabolism; Mice; MicroRNAs/*biosynthesis; NF-kappa B/*metabolism; Osteoblasts/*metabolism; Osteogenesis/drug effects; RAW 264.7 Cells; Silicic Acid/*pharmacology
UNLABELLED: Accumulating evidence over the last 40years suggests that silicate from dietary as well as silicate-containing biomaterials is beneficial to bone formation. However, the exact biological role(s) of silicate on bone cells are still unclear and controversial. Here, we report that orthosilicic acid (Si(OH)4) stimulated human mesenchymal stem cells (hMSCs) osteoblastic differentiation in vitro. To elucidate the possible molecular mechanisms, differential microRNA microarray analysis was used to show that Si(OH)4 significantly up-regulated microRNA-146a (miR-146a) expression during hMSC osteogenic differentiation. Si(OH)4 induced miR-146a expression profiling was further validated by quantitative RT-PCR (qRT-PCR), which indicated miR-146a was up-regulated during the late stages of hMSC osteogenic differentiation. Inhibition of miR-146a function by anti-miR-146a suppressed osteogenic differentiation of MC3T3 pre-osteoblasts, whereas Si(OH)4 treatment promoted osteoblast-specific genes transcription, alkaline phosphatase (ALP) production, and mineralization. Furthermore, luciferase reporter assay, Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence showed that Si(OH)4 decreased TNFalpha-induced activation of NF-kappaB, a signal transduction pathway that inhibits osteoblastic bone formation, through the known miR-146a negative feedback loop. Our studies established a mechanism for Si(OH)4 to promote osteogenesis by antagonizing NF-kappaB activation via miR-146a, which might be interesting to guide the design of osteo-inductive biomaterials for treatments of bone defects in humans. STATEMENT OF SIGNIFICANCE: Accumulating evidence over 40years suggests that silicate is beneficial to bone formation. However, the biological role(s) of silicate on bone cells are still unclear and controversial. Here, we report that Si(OH)4, the simplest form of silicate, can stimulate human mesenchymal stem cells osteoblastic differentiation. We identified that miR-146a is the expression signature in bone cells treated with Si(OH)4. Further analysis of miR-146a in bone cells reveals that Si(OH)4 upregulates miR-146a to antagonize the activation of NF-kappaB. Si(OH)4 was also shown to deactivate the same
Zhou Xianfeng; Moussa Fouad M; Mankoci Steven; Ustriyana Putu; Zhang Nianli; Abdelmagid Samir; Molenda Jim; Murphy William L; Safadi Fayez F; Sahai Nita
Acta biomaterialia
2016
2016-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.actbio.2016.05.007" target="_blank" rel="noreferrer noopener">10.1016/j.actbio.2016.05.007</a>
Myocardial CXCR4 expression is required for mesenchymal stem cell mediated repair following acute myocardial infarction.
Animals; Apoptosis/physiology; Cardiac/cytology/physiology; Cell Movement/physiology; Chemokine CXCL12/*metabolism; Coronary Circulation/physiology; CXCR4/*genetics/metabolism; Gene Expression/physiology; Green Fluorescent Proteins/genetics; Inbred C57BL; Knockout; Mesenchymal Stem Cell Transplantation/*methods; Mesenchymal Stem Cells/*metabolism; Mice; Myocardial Infarction/genetics/pathology/*therapy; Myocardium/cytology; Myocytes; Paracrine Communication/physiology; Receptors; Ventricular Remodeling/physiology
BACKGROUND: Overexpression of stromal cell-derived factor-1 in injured tissue leads to improved end-organ function. In this study, we quantify the local trophic effects of mesenchymal stem cell (MSC) stromal cell-derived factor-1 release on the effects of MSC engraftment in the myocardium after acute myocardial infarction. METHODS AND RESULTS: Conditional cardiac myocyte CXCR4 (CM-CXCR4) null mice were generated by use of tamoxifen-inducible cardiac-specific cre by crossing CXCR4 floxed with MCM-cre mouse. Studies were performed in littermates with (CM-CXCR4 null) or without (control) tamoxifen injection 3 weeks before acute myocardial infarction. One day after acute myocardial infarction, mice received 100,000 MSC or saline via tail vein. We show alpha-myosin heavy chain MerCreMer and the MLC-2v promoters are active in cardiac progenitor cells. MSC engraftment in wild-type mice decreased terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling positive CM (-44%, P\textless0.01), increased cardiac progenitor cell recruitment (100.9%, P\textless0.01), and increased cardiac myosin-positive area (39%, P\textless0.05) at 4, 7, and 21 days after acute myocardial infarction, respectively. MSC in wild-type mice resulted in 107.4% (P\textless0.05) increase in ejection fraction in comparison with 25.9% (P=NS) increase in CM-CXCR4 null mice. These differences occurred despite equivalent increases (16%) in vascular density in response to MSC infusion in wild-type and
Dong Feng; Harvey James; Finan Amanda; Weber Kristal; Agarwal Udit; Penn Marc S
Circulation
2012
2012-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1161/CIRCULATIONAHA.111.082453" target="_blank" rel="noreferrer noopener">10.1161/CIRCULATIONAHA.111.082453</a>