TITLE

Disease-associated extracellular matrix suppresses osteoblastic differentiation of human periodontal ligament cells via MMP-1

AUTHOR(S)
Joseph, Jeena; Kapila, Yvonne L.; Hayami, Takayuki; Kapila, Sunil
PUB. DATE
February 2010
SOURCE
Calcified Tissue International;Feb2010, Vol. 86 Issue 2, p154
SOURCE TYPE
Academic Journal
DOC. TYPE
journal article
ABSTRACT
Fibronectin (FN) fragments found in chronic inflammatory diseases, including periodontal disease and arthritis, may contribute to tissue destruction in part via induction of matrix metalloproteinases (MMPs). We previously showed that the 120-kDa FN fragment containing the central cell binding domain (120FN) dose dependently induces MMP-1 (collagenase-1) in human periodontal ligament (PDL) cells, whereas intact FN did not elicit this response. Recently, we found that an increase in MMP-1 expression is accompanied by a decreased osteoblastic phenotype in PDL cells. We hypothesized that 120FN inhibits osteoblastic differentiation of PDL cells by inducing MMP-1. Effects of increasing concentrations of 120FN on MMP-1 expression and on osteoblastic markers were assessed in cultured PDL cells using Western blotting, qRT-PCR, and collagen degradation and alkaline phosphatase (AP) activity assays. The 120FN dose dependently increased MMP-1 expression and activity, concomitant with a decrease in AP activity. The increase in collagenase activity was largely attributed to increased MMP-1 expression. Concurrent with the decrease in AP activity, the 120FN reduced baseline and dexamethasone-induced gene expression of specific osteoblastic markers, Runx2 and osteonectin, and diminished mineralized nodule formation. Finally, siRNA inhibition of 120FN-induced MMP-1 reduced collagenase expression and rescued the AP phenotype to baseline levels. These findings suggest that disease-associated 120FN, in addition to having direct effects on tissue destruction by upregulating MMPs, could contribute to disease progression by impeding osteoblastic differentiation of osteogenic PDL cells and, consequently, diminish bone regeneration.
ACCESSION #
47626436

 

Related Articles

  • Expression of Fibronectin and Integrins in Cultured Periodontal Ligament Epithelial Cells. UITTO, V.-J.; LARJAVA, H.; PELTONEN, J.; BRUNETTE, D. M. // Journal of Dental Research;May1992, Vol. 71 Issue 5, p1203 

    The process of attachment of epithelial cells obtained from the porcine periodontal ligament (cell rests of Malassez) to different extracellular matrix proteins and their expression of fibronectin and integrin receptors were studied by means of immunocytochemistry, in situ hybridization, and...

  • Extracellular Matrix Molecules Improve Periodontal Ligament Cell Adhesion to Anorganic Bone Matrix. Lallier, T. E.; Yukna, R.; Moses, R. L. // Journal of Dental Research;Aug2001, Vol. 80 Issue 8, p1748 

    Bone replacement graft (BRG) materials are used in periodontal therapy to encourage new bone formation. Extracellular matrix proteins may improve periodontal ligament fibroblast (PDLF) attachment to these materials. We demonstrate that PDLFs adhere well to the extracellular matrix (ECM) proteins...

  • Repair of bone defects using synthetic mimetics of collagenous extracellular matrices. Lutolf, Matthias P.; Weber, Franz E.; Schmoekel, Hugo G.; Schense, Jason C.; Kohler, Thomas; Muller, Ralph; Hubbell, Jeffrey A. // Nature Biotechnology;May2003, Vol. 21 Issue 5, p513 

    We have engineered synthetic poly(ethylene glycol) (PEG)-based hydrogels as cell-ingrowth matrices for in situ bone regeneration. These networks contain a combination of pendant oligopeptide ligands for cell adhesion (RGDSP) and substrates for matrix metalloproteinase (MMP) as linkers between...

  • Mesangial cell behavior in a three-dimensional extracellular matrix. Kitamura, Masanori; Mitarai, Tetsuya; Maruyama, Naoki; Nagasawa, Ryuji; Yoshida, Hiroaki; Sakai, Osamu // Kidney International;Oct1991, Vol. 40 Issue 4, p653 

    To understand the role of mesangial matrix in regulating responses of mesangial cells (MCs), particularly as a cause of disease, we examined the behavior of MCs cultured in a three-dimensional extracellular matrix (ECM). Mouse and rat MCs were incorporated into ECM composed of type I collagen...

  • Bone Repair Using Periodontal Ligament Progenitor Cell-seeded Constructs. Tour, G.; Wendel, M.; Moll, G.; Tcacencu, I. // Journal of Dental Research;Aug2012, Vol. 91 Issue 8, p789 

    The success of tissue-engineering therapies is dependent on the ability of scaffolds to guide differentiation of progenitor cells. Here we present a new approach using a biomimetic construct composed of hydroxyapatite modified with an in vitro-derived extracellular matrix (HA-ECM) and seeded...

  • Flow Cytometry Analysis of Gingival and Periodontal Ligament Cells. Kuru, L.; Parkar, M. H.; Griffiths, G. S.; Newman, H. N.; Olsen, I. // Journal of Dental Research;Apr1998, Vol. 77 Issue 4, p555 

    Gingival and periodontal ligament (PDL) fibroblasts are the major cellular components of periodontal soft connective tissues, but the precise differences between these cells are not yet known. In the present study, we have therefore examined the phenotypic and functional features of the cells...

  • Function of gingival fibroblasts and periodontal ligament cells in the presence of methyl mercaptan. Johnson, Paul W.; Lancero, Hope // Quintessence International;May1999, Vol. 30 Issue 5, p343 

    Objective: This study examined the effects of methyl mercaptan, a product of the bacterial putrefaction of protein in periodontal pockets, on the function of cells in culture. Method and materials: Human gingival fibroblasts and periodontal ligament cells were exposed to a constant, continuous...

  • Rebuild your body. Coghlan, Andy // New Scientist;9/14/2013, Vol. 219 Issue 2934, p32 

    The article looks at biomedical engineering research into the regeneration of damaged or diseased tissues and organs with the use of extracellular matrix cellular scaffolding. The extracellular matrix contains fibronectin and integrin proteins targeted towards types of cells, and can promote...

  • Engineering of a multi-functional extracellular matrix protein for immobilization to bone mineral hydroxyapatite. Kang, Wonmo; Kim, Tai-Il; Yun, Yerang; Kim, Hae-Won; Jang, Jun-Hyeog // Biotechnology Letters;Jan2011, Vol. 33 Issue 1, p199 

    Purpose of Work: We have developed a strategy of designing multi-functional extracellular matrix proteins for functionalizing bone tissue engineering scaffolds and other biomedical surfaces to achieve improvements in bone grafting, bone repair and bone regeneration. We developed a novel...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics