Nagarajan Selvamurugan

SRM University, Chennai, Tamil Nādu, India

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Publications (67)255.97 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Wollastonite (calcium silicate) has been widely used in bone tissue engineering, but its mechanism of action on the regulation of mesenchymal stem cell proliferation and differentiation to osteoblasts still remains unclear. The current study utilized an inexpensive source of rice straw ash to synthesize wollastonite with mesoporous architecture. Mesoporous-wollastonite (m-WS) particles were characterized by transmission electron microscopy (TEM), N2 adsorption–desorption isotherms, and Fourier transform infrared (FT-IR) spectroscopy. These particles were found to be biocompatible with mouse mesenchymal stem cells (C3H10T1/2) and significantly stimulated cell proliferation by promoting the entry of the cell population from the G0/G1 phase into the S and G2/M phases via the upregulated expression of the cyclin B1 and cyclin E genes. Under osteogenic conditions, m-WS particles promoted osteoblast differentiation as indicated by calcium deposits and upregulated mRNA expression of osteoblast differentiation marker genes determined by real-time RT-PCR, depicting the osteoconductive nature of these particles. Runx2, a bone-specific transcription factor responsible for the expression of osteoblast differentiation marker genes, was upregulated in C3H10T1/2 cells. The expression of Runx2 co-regulators like Sirt-1, a positive regulator, and HDAC-4, a negative regulator, were upregulated and downregulated, respectively, by m-WS particles in these cells. Thus, this study provides a detailed insight into the effect of m-WS particles on mesenchymal stem cells at the molecular and cellular levels for in vitro bone formation.
    Journal of Biomedical Nanotechnology 07/2015; 11(7). · 7.58 Impact Factor
  • M Gokulnath, N C Partridge, N Selvamurugan
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    ABSTRACT: Activating transcription factor (ATF-3) is a stress response gene and is induced by transforming growth factor beta 1 (TGF-β1) in breast cancer cells. In this study, we dissected the functional role of ATF-3 gene in vitro by knocking down its expression stably in human bone metastatic breast cancer cells (MDA-MB231). Knockdown of ATF-3 expression in these cells decreased cell number, altered cell cycle phase transition, and decreased mRNA expression of cell cycle genes. Knockdown of ATF-3 expression in MDA-MB231 cells also decreased cell migration, and the expression levels of invasive and metastatic genes such as MMP-13 and Runx2 were found to be decreased in these cells. Most importantly, ATF-3 was associated with Runx2 promoter in MDA-MB231 cells and knockdown of ATF-3 expression decreased its association with Runx2 promoter. Hence, our results suggested that ATF-3 plays a role in proliferation and invasion of bone metastatic breast cancer cells in vitro and we identified for the first time that Runx2 is a target gene of ATF-3 in MDA-MB231 cell line.
    Tumor Biology 11/2014; · 2.84 Impact Factor
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    ABSTRACT: 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. The synthesized nBGC particles were characterized by transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) studies. They exhibited their size at nanoscale and were non-toxic to human osteoblastic cells (MG-63). The nBGC-2 particles were found to have more effect on stimulation of osteoblast proliferation and promoted entering of more cells into G2/M cell cycle phase compared to nBGC-1 particles. There was a differential expression of cyclin proteins in MG-63 cells by nBGC-1 and nBGC-2 treatments, and the expression of cyclin B1 and E proteins was found to be more by nBGC-2 treatment. Thus, these results provide us a new insight in understanding the design of various nBGC particles by altering their ionic constituents with desirable biological properties thereby supporting bone augmentation.
    Materials Science and Engineering C 10/2014; 43C:458-464. · 2.74 Impact Factor
  • P J Miranda, S Vimalraj, N Selvamurugan
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    ABSTRACT: MicroRNAs (miRNAs) are small non coding RNA molecules (∼23nt) that are capable of regulating several physiological and pathological processes by targeting mRNAs post transcriptionally, and miRNAs are also known to be regulated by their own target gene(s) in a feedback manner. In this study, we analysed the expression of miRNAs (pre-mir-93, pre-mir-20b, pre-mir-520c, pre-mir-143, pre-mir-154 and pre-mir-590) by body map, an in silico method and by qRT-PCR in MDA-MB231 (highly invasive and metastatic in nature), and MCF-7 (poor invasive and metastatic in nature) cells. These miRNAs were down regulated in MDA-MB231 cells, and among these, miR-590 was found to putatively target activating transcription factor-3 (ATF-3), a stress response gene. ATF-3 expression level was significantly increased in MDA-MB231 cells and inhibition of ATF-3 expression in these cells increased the expression of pre-mir-590. Thus, these results suggest that there is a negative feedback expression of pre-mir-590 and its putative target gene, ATF-3 in human breast cancer cells.
    International Journal of Biological Macromolecules 08/2014; · 3.10 Impact Factor
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    ABSTRACT: The scaffolds for bone tissue engineering should be porous to harbor the growth of new tissue ingrowths, biodegradable with no toxic end products, and biocompatible with no cytotoxicity. In this study we report that Diopside (CaMgSi2O6) (Dp) particles can be synthesized at a more economical route using the agricultural waste rice straw. Along with chitosan (CS) matrix, the CS/Dp scaffolds were synthesized and evaluated for their physico-chemical properties by SEM, EDS, XRD, FT-IR studies. Addition of Dp particles to chitosan matrix decreased water retention capacity but there was no change in their degradation properties. Dp particles in CS/Dp scaffolds exhibited good affinity for protein adsorption. Apatite forming ability of the CS/Dp scaffolds depicted their bioactivity. These scaffolds were found to be compatible with human osteoblastic cells (MG-63) and the cells were able to attach and proliferate with extended morphology on the CS/Dp membranes. The CS/Dp scaffolds supported up regulation of mRNA expression of osteoblast differentiation marker genes such alkaline phosphatase (ALP), type I collagen (COL-I) in the presence of osteogenic environment suggesting their osteo-conductive nature. In vivo rat model system identified that the CS/Dp scaffolds are biocompatible and may have the property of recruiting cells due to deposition of collagen. Hence, these studies suggest that the prepared CS/Dp scaffolds have potential applications towards bone tissue engineering.
    Journal of Biomedical Nanotechnology 06/2014; 10(6):970-81. · 7.58 Impact Factor
  • S Vimalraj, N Selvamurugan
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    ABSTRACT: MicroRNAs (miRNAs) are small endogenous non coding 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) towards 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. A bioinformatics approach identified that the MAPK pathway was mostly targeted by hMSCs specific miRNAs; whereas JAK-STAT, p53, Focal adhesion, Gap junction, Ubiquitin mediated proteolysis pathways were targeted by osteblastic specific miRNAs. Altering expression of osteoblast specific miRNA (miR-15b) promoted adipogenesis and myogenesis lineages. Thus, we suggest that miRNAs' regulatory networks and their target genes might provide an insight of their role during differentiation of hMSCs towards osteoblasts, and alteration in the expression of miRNAs would be a valuable approach for controlling osteoblast differentiation.
    International journal of biological macromolecules 02/2014; · 2.37 Impact Factor
  • S Vimalraj, Nicola C Partridge, N Selvamurugan
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    ABSTRACT: Osteoblast differentiation is tightly regulated by several factors including microRNAs (miRNAs). In this paper we report that pre-mir-15b is highly expressed in differentiated osteoblasts. The functional role of miR-15b in osteoblast differentiation was determined using miR-15b mimic/inhibitor and the expression of osteoblast differentiation marker genes such as alkaline phosphatase (ALP), type I collagen genes was decreased by miR-15b inhibitor. Runx2, a bone specific transcription factor is generally required for expression of osteoblast differentiation marker genes and in response to miR-15b inhibitor treatment, Runx2 mRNA expression was not changed; whereas its protein expression was decreased. Even though Smurf1 (SMAD specific E3 ubiquitin protein ligase 1), HDAC4 (histone deacetylase 4), Smad7, and Crim1 were found to be few of miR-15b's putative target genes, there was increased expression of only Smurf1 gene at mRNA and protein levels by miR-15b inhibitor. miR-15b mimic treatment significantly increased and decreased expressions of Runx2 and Smurf1 proteins, respectively. We further identified that the Smurf1 3'UTR is directly targeted by miR-15b using the luciferase reporter gene system. This is well documented that Smurf1 interacts with Runx2 and degrades it by proteasomal pathway. Hence, based on our results we suggest that miR-15b promotes osteoblast differentiation by indirectly protecting Runx2 protein from Smurf1 mediated degradation. Thus, this study identified that miR-15b can act as a positive regulator for osteoblast differentiation.
    Journal of Cellular Physiology 01/2014; · 3.87 Impact Factor
  • S Saravanan, D.K. Sameera, A Moorthi, N Selvamurugan
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    ABSTRACT: Chicken feathers are considered as major waste from poultry industry. They are mostly constituted by a protein called keratin. In this study, keratin was prepared from chicken feathers and from where keratin nanoparticles (nKer) were synthesized. Since chitosan has excellent properties like controlled biodegradation and biocompatibility, we used keratin nanoparticles along with chitosan matrix as scaffolds (CS/nKer) and they were characterized by SEM, FT-IR and XRD analyses. There was a porous architecture in the scaffolds in the range to support cell infiltration and tissue ingrowth. The keratin nanoparticles had interaction with chitosan matrix and did not alter the semi crystalline nature of chitosan scaffolds. The biodegradation and protein adsorption of the scaffolds were significantly increased upon addition of keratin nanoparticles. The scaffolds were also found to be non-cytotoxic to human osteoblastic cells. Thus, CS/nKer scaffolds could serve as a potential biomimetic substrate for bone tissue engineering applications.
    International journal of biological macromolecules 10/2013; · 2.37 Impact Factor
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    ABSTRACT: Growth factor signaling plays a key role in the growth and development of breast. Aberrant expression and activation of growth factors like insulin like growth factor-I (IGF-I) and epidermal growth factor (EGF) and their downstream sig-naling has been implicated in breast cancer. The deregulation of growth factor signaling is associated with increased proliferation and cell survival, decreased apoptosis, invasion, angiogenesis and metastasis. The aim of the present study is to survey the different signaling molecules involved in the IGF and EGF signaling pathways, and to find if there are any relationship between breast cancer and their levels and activation. Thirty-nine samples of breast cancer tissues (24 Grade II and 15 Grade III tumours) and sixteen normal breast tissue samples were collected. The expression of the re-ceptors and signaling molecules were investigated using Western blot. IGF-IRβ, AR, pAkt, IKK-α and p38 are upregu-lated in cancer tissues in a grade depended manner. Further, Akt and β-catenin were also upregulated in cancer samples. Correlation analysis of signaling molecules revealed a disruption in their expression in cancer tissues. The present study shows that various signaling molecules are upregulated or activated in cancer tissues involving IGF-IR and Akt path-way. The expression of signaling molecules in the cancer tissues were deregulated when compared to the control sam-ples. Thus, flawed expression and over activation of Akt pathway is seen in the breast cancer tissues.
    Journal of Cancer Therapy 06/2013; 4(07).
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    ABSTRACT: Bone tissue engineering is a promising alternative method for treating bone loss by a combination of biomaterials and cells. In this study, we fabricated biocomposite scaffolds by blending chitosan (CS), alginate (Alg) and nano-silica (nSiO2), followed by freeze drying. The prepared scaffolds (CS/Alg, CS/Alg/nSiO2) were characterized by SEM, FT-IR and XRD analyses. In vitro studies such as swelling, biodegradation, biomineralization, protein adsorption and cytotoxicity were also carried out. The scaffolds possessed a well-defined porous architecture with pore sizes varying from 20 to 100μm suitable for cell infiltration. The presence of nSiO2 in the scaffolds facilitated increased protein adsorption and controlled swelling ability. The scaffolds were biodegradable and the addition of nSiO2 improved apatite deposition on these scaffolds. There was no significant cytotoxicity effect of these CS/Alg/nSiO2 scaffolds towards osteolineage cells. Thus, these results indicate that CS/Alg/nSiO2 scaffolds may have potential applications for bone tissue engineering.
    Colloids and surfaces B: Biointerfaces 04/2013; 109C:294-300. · 4.28 Impact Factor
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    ABSTRACT: BACKGROUND: Breast cancer is the most common cancer affecting women in the world today. Matrix metalloproteinases (MMPs) are a family of endopeptidases that can degrade extracellular matrix proteins and promote cell invasion and metastasis. MMPs are differentially expressed and their expressions are often associated with a poor prognosis for patients.OBJECTIVE: The aim of this study is to investigate and compare the expression of MMPs in different grades of human breast cancer tissues with normal breast tissues. PATIENTS AND METHODS: We collected 39 breast cancer samples (24 grade II and 15 grade III) along with 16 normal breast tissues from outside the tumor margin during cancer removal surgery. The samples were analysed for the expression of all known MMPs using real-time quantitative PCR. RESULTS: The results indicate that mRNA expressions of MMP-1, -9,-11,-15,-24 and -25 were upregulated in breast cancer tissues when compared to normal breast tissues. But, the mRNA expressions of MMP-10 and MMP-19 were downregulated in cancer tissue. In membrane associated MMPs like MMP-15 and MMP-24 we found a grade dependent increase of their mRNA expression. CONCLUSION: Our studies demonstrate that MMPs are differentially regulated in breast cancer tissues and they might play various roles in tumor invasion, metastasis and angiogenesis. Thus, MMPs are of immense value to be studied as diagnostic markers and drug target.
    Disease markers 04/2013; · 2.17 Impact Factor
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    ABSTRACT: Osteoblast differentiation is tightly regulated by post transcriptional regulators such as microRNAs (miRNAs). Several bioactive materials including nano-bioglass ceramic particles (nBGC) influence differentiation of the osteoblasts, but the molecular mechanisms of nBGC-stimulation of osteoblast differentiation via miRNAs are not yet determined. In this study, we identified that nBGC-treatment stimulated miR-30c expression in human osteoblastic cells (MG63). The bioinformatics tools identified its regulatory network, molecular function, biological processes and its target genes involved in negative regulation of osteoblast differentiation. TGIF2 and HDAC4 were found to be its putative target genes and their expression was down regulated by nBGC-treatment in MG63 cells. Thus, this study advances our understanding of nBGC action on bone cells and supports utilization of nBGC in bone tissue engineering.
    International journal of biological macromolecules 03/2013; · 2.37 Impact Factor
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    ABSTRACT: Breast cancer progression including bone metastasis is a complex process involving numerous changes in gene expression and function. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that regulate gene expression by targeting protein-coding mRNAs posttranscriptionally, often affecting a number of gene targets simultaneously. Alteration in expression of miRNAs is common in human breast cancer, possessing with either oncogenic or tumor suppressive activity. The expression and the functional role of several miRNAs (miR-206, miR-31, miR-27a/b, miR-21, miR-92a, miR-205, miR-125a/b, miR-10b, miR-155, miR-146a/b, miR-335, miR-204, miR-211, miR-7, miR-22, miR-126, and miR-17) in breast cancer has been identified. In this review we summarize the experimentally validated targets of up- and downregulated miRNAs and their regulation in breast cancer and bone metastasis for diagnostic and therapeutic purposes.
    Disease markers 01/2013; 35(5):369-387. · 2.17 Impact Factor
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    ABSTRACT: Hydrogels are hydrophilic polymers that have a wide range of biomedical applications including bone tissue engineering. In this study we report preparation and characterization of a thermosensitive hydrogel (Zn-CS/β-GP) containing Zinc (Zn), Chitosan (CS) and Beta-glycerophosphate (β-GP) for bone tissue engineering. The prepared hydrogel exhibited a liquid state at room temperature and turned into a gel at body temperature. The hydrogel was characterized by SEM, EDX, XRD, FT-IR and swelling studies. The hydrogel enhanced antibacterial activity and promoted osteoblast differentiation. Thus, we suggest that the Zn-CS/β-GP hydrogel could have potential impact as an injectable in-situ forming scaffold for bone tissue engineering applications.
    International journal of biological macromolecules 11/2012; · 2.37 Impact Factor
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    S Vimalraj, N Selvamurugan
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    ABSTRACT: The central dogma of transfer of genetic information from DNA to protein via mRNA is now challenged by small fragment of non coding RNAs typically 19-25 nucleotides in length namely microRNAs (miRNAs). miRNAs regulate expression of the protein coding genes by interfering in their mRNAs and, thus, act as key regulators of diverge cellular activities. Osteoblast differentiation, a key step in skeletal development involves activation of several signalling pathways including TGFb, BMP, Wnt and transcription factors, which are tightly regulated by miRNAs. In this review, we provide information on recent developments of the synthesis and gene regulation of miRNAs as well as the potential nature of miRNAs that regulate mesenchymal stem cell towards osteoblast differentiation for therapeutic purpose.
    Current issues in molecular biology 05/2012; 15(1):7-18. · 6.00 Impact Factor
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    ABSTRACT: Current research work was aimed at evaluating the role of nano bioglass ceramic (nBGC) parti-cles for bone formation. The nBGC particles were synthesized by sol–gel method and they were characterized by TEM, EDS, FT-IR and XRD studies. These particles were found to be non toxic to rat osteoprogenitor cells and were able to stimulate proliferation of the cells. Intracellular ERK signaling pathways as well as cell cycle gene expression (cyclin C) in rat osteoprogenitor cells were stimulated by nBGC particles. Osteoprogenitor or preosteoblastic cells were differentiated and min-eralized by nBGC particles and this effect required the presence of osteogenic stimulants. Runx2, a bone specific transcription factor controlling expression of osteoblast differentiation genes was also stimulated by nBGC particles. Hence, our results suggest that nBGC particles promote bone formation by cell proliferation and differentiation, and the effect of nBGC particles on osteoblast differentiation is possibly mediated by Runx2 within the osteogenic environment.
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    ABSTRACT: The bone implants used in tissue repair are susceptible to infections caused by staphylococci, specifically Staphylococcus aureus. Hence, the development of better biological materials that provide antimicrobial activity in bone tissue engineering is required. The nanoparticles of hydroxyapatite (nHAp) and nHAp dopped with Zn (nHAp-Zn) were prepared by the wet chemical method and the ion exchange method, respectively. They were characterized using SEM, AFM, FTIR and XRD. The antibacterial activity of nHAp and nHAp-Zn was determined with Gram-negative and Gram-positive bacterial strains. The results indicated that nHAp alone was acting as an inert matrix and when substituted with Zn, it showed better antibacterial activity. The nHAp-Zn was found to be non-toxic to osteoprogenitor cells. Thus, due to the antimicrobial property of nHAp-Zn nanoparticles, we suggest that they would have potential applications towards bone tissue engineering.
    Journal of Nanoscience and Nanotechnology 01/2012; 12(1):167-72. · 1.34 Impact Factor
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    ABSTRACT: The current study involves fabrication and characterization of bio-composite scaffolds containing chitosan (CS), nano-hydroxyapatite (nHAp) and Cu-Zn alloy nanoparticles (nCu-Zn) by freeze drying technique. The fabricated composite scaffolds (CS/nHAp and CS/nHAp/nCu-Zn) were characterized by SEM, EDX, XRD and FT-IR studies. The addition of nCu-Zn in the CS/nHAp scaffolds significantly increased swelling, decreased degradation, increased protein adsorption, and increased antibacterial activity. The CS/nHAp/nCu-Zn scaffolds had no toxicity towards rat osteoprogenitor cells. So the developed CS/nHAp/nCu-Zn scaffolds have advantageous and potential applications over the CS-nHAp scaffolds for bone tissue engineering.
    International journal of biological macromolecules 11/2011; 50(1):294-9. · 2.37 Impact Factor
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    ABSTRACT: A scaffold harboring the desired features such as biodegradation, biocompatibility, porous structure could serve as template for bone tissue engineering. In the present study, chitosan (CS), nano-scaled silicon dioxide (Si) and zirconia (Zr) were combined by freeze drying technique to fabricate a bio-composite scaffold. The bio-composite scaffold (CS/Si/Zr) was characterized by SEM, XRD and FT-IR studies. The scaffold possessed a porous nature with pore dimensions suitable for cell infiltration and colonization. The presence of zirconia in the CS/Si/Zr scaffold decreased swelling and increased biodegradation, protein adsorption and bio-mineralization properties. The CS/Si/Zr scaffold was also found to be non-toxic to rat osteoprogenitor cells. Thus, we suggest that CS/Si/Zr bio-composite scaffold is a potential candidate to be used for bone tissue engineering.
    International journal of biological macromolecules 09/2011; 49(5):1167-72. · 2.37 Impact Factor

Publication Stats

2k Citations
255.97 Total Impact Points


  • 2010–2013
    • SRM University
      • School of Bio-Engineering
      Chennai, Tamil Nādu, India
    • Amrita Vishwa Vidyapeetham
      • Amrita Center for Nanosciences & Molecular Medicine (ACNSMM)
      Koyambattūr, Tamil Nādu, India
    • New York University College of Dentistry
      New York City, New York, United States
  • 2009–2011
    • University of Madras
      • Department of Endocrinology
      Chennai, Tamil Nādu, India
  • 2009–2010
    • Kansai University
      • Faculty of Chemistry, Materials and Bioengineering
      Suita, Osaka-fu, Japan
  • 2002–2009
    • Robert Wood Johnson University Hospital
      New Brunswick, New Jersey, United States
  • 2008
    • Amrita Institute of Medical Sciences and Research Centre
      • Center for Nanosciences and Molecular Medicine
      Fort Cochin, Kerala, India
  • 1995–2000
    • Washington University in St. Louis
      San Luis, Missouri, United States
    • University of Missouri - St. Louis
      Saint Louis, Michigan, United States