Stimulation of ATF3 interaction with Smad4 via TGF-β1 for matrix metalloproteinase 13 gene activation in human breast cancer cells.

We previously reported that transforming growth factor-β1 (TGF-β1) stimulated the sustained and prolonged expression of activating transcription factor 3 (ATF3) in highly metastatic and invasive human breast cancer cells (MDA-MB231), in contrast to normal human mammary epithelial cells. However, the mechanism behind the stability of ATF3 expression is not yet known. Based on an in silico approach with co-immunoprecipitation and mass spectrometric analyses, we identified a number of proteins, including Smad4, that interacted with ATF3 after TGF-β1 treatment in MDA-MB231 cells.

Sinapic acid-loaded chitosan nanoparticles in polycaprolactone electrospun fibers for bone regeneration in vitro and in vivo.

Sinapic acid (SA) is a plant-derived phenolic compound known for its multiple biological properties, but its role in the promotion of bone formation is not yet well-studied. Moreover, the delivery of SA is hindered by its complex hydrophobic nature, limiting its bioavailability. In this study, we fabricated a drug delivery system using chitosan nanoparticles (nCS) loaded with SA at different concentrations.

Chitosan and gelatin-based electrospun fibers for bone tissue engineering.

Fractures and injuries pertaining to bone tissue usually take prolonged periods for its natural healing. To overcome this problem, the field of bone tissue engineering (BTE) has acquired an efficient designing mechanism that incorporates cells, biomaterials and the corresponding growth factors to promote both osteogenesis as well as mineralization of the bone. Amidst the various techniques available for scaffold creation, electrospinning is considered superior as it paves the way for the creation of nanostructured scaffolds using biopolymers.

TGF-β1-stimulation of matrix metalloproteinase-13 expression by down-regulation of miR-203a-5p in rat osteoblasts.

Transforming growth factor-beta1 (TGF-β1) is a pleiotropic and ubiquitous cytokine involved in bone development and bone remodeling. Matrix metalloproteinase-13 (MMP13) plays a role in the degradation of the extracellular matrix (ECM), and the regulation of this gene is critical in bone remodeling. We previously reported that TGF-β1 stimulates MMP13 expression in rat osteoblasts.

Parathyroid hormone-stimulation of Runx2 during osteoblast differentiation via the regulation of lnc-SUPT3H-1:16 (RUNX2-AS1:32) and miR-6797-5p.

Parathyroid hormone (PTH) acts as a regulator of calcium homeostasis and bone remodeling. Runx2, an essential transcription factor in bone, is required for osteoblast differentiation. Noncoding RNAs such as long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play crucial roles in regulating gene expression in osteoblasts.

Role of activating transcription factor 3 and its interacting proteins under physiological and pathological conditions.

Activating transcription factor 3 (ATF3) is a stress-responsive factor that belongs to the activator protein 1 (AP-1) family of transcription factors. ATF3 expression is stimulated by various factors such as hypoxia, cytokines, and chemotherapeutic and DNA damaging agents. Upon stimulation, ATF3 can form homodimers or heterodimers with other members of the AP-1 family to repress or activate transcription.

Fabrication of PCL/PVP Electrospun Fibers loaded with Trans-anethole for Bone Regeneration in vitro.

Trans-anethole (TA) is a phenolic phytocompound widely used in the food and health sector because of its diverse biological properties. However, its role in the promotion of bone formation is not known. With the enhanced bioavailability of TA, we aimed to determine its effect on osteogenesis; TA at different concentrations (5, 10, and 20 μM) was loaded onto polycaprolactone (PCL)/polyvinylpyrrolidone (PVP) fibers by the electrospinning technique.

Bone tissue engineering: Scaffold preparation using chitosan and other biomaterials with different design and fabrication techniques.

In the recent years, a paradigm shift is taking place where metallic/synthetic implants and tissue grafts are being replaced by tissue engineering approach. A well designed three-dimensional scaffold is one of the fundamental tools to guide tissue formation in vitro and in vivo. Bone is a highly dynamic and an integrative tissue, and thus enormous efforts have been invested in bone tissue engineering to design a highly porous scaffold which plays a critical role in guiding bone growth and regeneration.

miR-590-3p inhibits proliferation and promotes apoptosis by targeting activating transcription factor 3 in human breast cancer cells.

We previously reported that ATF3 and Runx2 are involved in breast cancer progression and bone metastasis. The expression of these genes can be controlled by post-transcriptional regulators such as microRNAs (miRNAs). In this study, we identified and validated the functional role of miR-590-3p in human breast cancer cells (MDA-MB231).

Sustained release of chrysin from chitosan-based scaffolds promotes mesenchymal stem cell proliferation and osteoblast differentiation.

Numerous phytochemical compounds have recently been reported to stimulate osteogenesis. In this study, the bioavailability and osteogenic effects of chrysin, a natural flavonoid, were investigated. Chrysin was incorporated at different concentrations into biocomposite scaffolds containing carboxymethyl cellulose, chitosan, and nano-hydroxyapatite, through the freeze-drying method.

Chitosan/nano-hydroxyapatite/nano-zirconium dioxide scaffolds with miR-590-5p for bone regeneration.

Bone tissue engineering (BTE) relies on biocomposite scaffolds and bioactive molecules for bone regeneration. The present study was aimed to synthesize and characterize biocomposite scaffolds containing chitosan (CS), nano-hydroxyapatite (nHAp) and nano‑zirconium dioxide (nZrO) along with microRNA (miRNA) for BTE applications. miRNAs act as post-transcriptional regulator of gene expression.

Matrix metalloproteinase-13: A special focus on its regulation by signaling cascades and microRNAs in bone.

Bone remodeling is an orchestrated process involving osteoblasts and osteoclasts to maintain mineral homeostasis in the internal milieu, mediated chiefly by matrix metalloproteinases (MMPs). MMP13, one amongst the MMPs plays a premier role in bone remodeling, and mutations in MMP13 have been implicated in various pathologies including cancer and arthritis. Transcriptional activation of MMP13 gene is tightly regulated by several signaling cascade components.

Natural and synthetic polymers/bioceramics/bioactive compounds-mediated cell signalling in bone tissue engineering.

Bone is a highly integrative and dynamic tissue of the human body. It is continually remodeled by bone cells such as osteoblasts, osteoclasts. When a fraction of a bone is damaged or deformed, stem cells and bone cells under the influence of several signaling pathways regulate bone regeneration at the particular locale.

Scaffolds containing chitosan, gelatin and graphene oxide for bone tissue regeneration in vitro and in vivo.

Critical-sized bone defects are augmented with cell free and cell loaded constructs to bridge bone defects. Improving the properties of three-dimensional scaffolds with multiple polymers and others is of growing interest in recent decades. Chitosan (CS), a natural biopolymer has limitations for its use in bone regeneration, and its properties can be enhanced with other materials.

Chitosan based nanofibers in bone tissue engineering.

Bone tissue engineering involves biomaterials, cells and regulatory factors to make biosynthetic bone grafts with efficient mineralization for regeneration of fractured or damaged bones. Out of all the techniques available for scaffold preparation, electrospinning is given priority as it can fabricate nanostructures. Also, electrospun nanofibers possess unique properties such as the high surface area to volume ratio, porosity, stability, permeability and morphological similarity to that of extra cellular matrix.

Transforming growth factor-β1 regulation of ATF-3, c-Jun and JunB proteins for activation of matrix metalloproteinase-13 gene in human breast cancer cells.

Transforming growth factor-beta1 (TGF-β1) plays a significant role in breast cancer mediated bone metastasis, and it stimulated expression of matrix metalloproteinase-13 (MMP-13; an invasive and metastasis gene) via activating transcription factor-3 (ATF-3) in human breast cancer cells (MDA-MB231). We further dissected the role of ATF-3 and its interacting proteins (activator protein-1; AP-1) for TGF-β1-stimulation of MMP-13 expression in these cells. Chromatin immunoprecipitation (ChIP) experiment identified the TGF-β1-stimulation of ATF-3 interaction at the AP-1 site of the MMP-13 promoter in a sustained and prolonged manner in MDA-MB231 cells.

Chitosan based biocomposite scaffolds for bone tissue engineering.

The clinical demand for scaffolds and the diversity of available polymers provide freedom in the fabrication of scaffolds to achieve successful progress in bone tissue engineering (BTE). Chitosan (CS) has drawn much of the attention in recent years for its use as graft material either as alone or in a combination with other materials in BTE. The scaffolds should possess a number of properties like porosity, biocompatibility, water retention, protein adsorption, mechanical strength, biomineralization and biodegradability suited for BTE applications.

A Combinatorial effect of carboxymethyl cellulose based scaffold and microRNA-15b on osteoblast differentiation.

The present study was aimed to synthesize and characterize a bio-composite scaffold containing carboxymethyl cellulose (CMC), zinc doped nano-hydroxyapatite (Zn-nHAp) and ascorbic acid (AC) for bone tissue engineering applications. The fabricated bio-composite scaffold was characterized by SEM, FT-IR and XRD analyses. The ability of scaffold along with a bioactive molecule, microRNA-15b (miR-15b) for osteo-differentiation at cellular and molecular levels was determined using mouse mesenchymal stem cells (mMSCs).

Scaffolds containing chitosan/carboxymethyl cellulose/mesoporous wollastonite for bone tissue engineering.

Scaffold based bone tissue engineering utilizes a variety of biopolymers in different combinations aiming to deliver optimal properties required for bone regeneration. In the current study, we fabricated bio-composite scaffolds containing chitosan (CS), carboxymethylcellulose (CMC) with varied concentrations of mesoporous wollastonite (m-WS) particles by the freeze drying method. The CS/CMC/m-WS scaffolds were characterized by the SEM, EDS and FT-IR studies.

Effect of size of bioactive glass nanoparticles on mesenchymal stem cell proliferation for dental and orthopedic applications.

Bioactive glass nanoparticles (nanostructured bioglass ceramics or nBGs) have been widely employed as a filler material for bone tissue regeneration. The physical properties of nBG particles govern their biological actions. In this study, the impact of the size of nBG particles on mouse mesenchymal stem cell (mMSC) proliferation was investigated.

Regulation of proliferation and apoptosis in human osteoblastic cells by microRNA-15b.

MicroRNAs (miRNAs) play an important role in proliferation and differentiation of osteoblasts. We recently reported that miR-15b acts as a positive regulator of osteoblast differentiation, whereas its functional role in osteoblastic proliferation remains not known. In this study, we found that there was increased proliferation of human osteoblastic cells (MG63) when they were transiently transfected with miR-15b inhibitor.

Runx2: Structure, function, and phosphorylation in osteoblast differentiation.

Runx2 is a master transcription factor for osteogenesis. The most important phenomenon that makes this protein a master regulator for osteogenesis is its structural integrity. In response to various stimuli, the domains in Runx2 interact with several proteins and regulate a number of cellular events via posttranslational modifications.

Biomaterials mediated microRNA delivery for bone tissue engineering.

Bone tissue engineering is an alternative strategy to overcome the problems associated with traditional treatments for bone defects. A number of bioactive materials along with new techniques like porous scaffold implantation, gene delivery, 3D organ printing are now-a-days emerging for traditional bone grafts and metal implants. Studying the molecular mechanisms through which these biomaterials induce osteogenesis is an equally hot field.

Effects of silica and calcium levels in nanobioglass ceramic particles on osteoblast proliferation.

At nanoscale, bioglass ceramic (nBGC) particles containing calcium oxide (lime), silica and phosphorus pentoxide promote osteoblast proliferation. However, the role of varied amounts of calcium and silica present in nBGC particles on osteoblast proliferation is not yet completely known. Hence, the current work was aimed at synthesizing two different nBGC particles with varied amounts of calcium oxide and silica, nBGC-1: SiO2:CaO:P2O5; mol%~70:25:5 and nBGC-2: SiO2:CaO:P2O5; mol%~64:31:5, and investigating their role on osteoblast proliferation.

MicroRNAs expression and their regulatory networks during mesenchymal stem cells differentiation toward osteoblasts.

MicroRNAs (miRNAs) are small endogenous noncoding RNAs which regulate mRNAs post-transcriptionally. In this study, a selective number of miRNAs was investigated for their expression and intracellular regulatory networks involved in differentiation of human mesenchymal stem cells (hMSCs) toward osteoblasts. The expression of miR-424, miR-106a, miR-148a, let-7i and miR-99a miRNAs was found to be specific in hMSCs; whereas expression of miR-15b, miR-24, miR-130b, miR-30c, and miR-130a miRNAs was found to be specific in differentiated osteoblasts.