Specific Pro‐Apoptotic Fibronectin Fragments Modulate Proteinase Expression in Periodontal Ligament Cells

Jee, Sang-Wook; Wang, Shaohui; Kapila, Yvonne L.

doi:10.1902/jop.2004.75.4.523

Cited by 10 publications

(9 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given that periodontal-disease-associated fibronectin fragments induce anoikis and MMP expression, and suppress osteoblastic differentiation in periodontal ligament fibroblasts, the present findings are relevant to periodontal inflammation and periodontal disease pathogenesis (Kapila et al, 1996;Huynh et al, 2002;Jee et al, 2004;Dai et al, 2005;Ghosh et al, 2008Ghosh et al, , 2010Joseph et al, 2010;Miao et al, 2011). In this context, our study demonstrates that inhibition of MMP-13 leads to significant increased NG2mediated cell death in periodontal ligament fibroblasts.…”

Section: Discussionsupporting

confidence: 54%

Shedding of NG2 by MMP-13 Attenuates Anoikis

Joo

Miao

Bermúdez

et al. 2014

DNA and Cell Biology

Self Cite

View full text Add to dashboard Cite

Disruption of cell-matrix interactions can lead to anoikis-apoptosis due to loss of matrix contacts. We previously showed that Nerve/glial antigen 2 (NG2) is a novel anoikis receptor. Specifically, overexpression of NG2 leads to anoikis propagation, whereas its suppression leads to anoikis attenuation. Interestingly, NG2 expression decreases in late anoikis, suggesting that NG2 reduction is also critical to this process. Thus, we hypothesized that NG2 undergoes cleavage to curtail anoikis propagation. Further, since matrix metalloproteinases (MMPs) cleave cell surface receptors, play a major role in modulating apoptosis, and are associated with death receptor cleavage during apoptosis, we further hypothesized that cleavage of NG2 could be mediated by MMPs to regulate anoikis. Indeed, anoikis conditions triggered release of the NG2 extracellular domain into condition media during late apoptosis, and this coincided with increased MMP-13 expression. Treatment with an MMP-13 inhibitor and MMP-13 siRNA increased anoikis, since these treatments blocked NG2 release. Further, NG2-positive cells exhibited increased anoikis upon MMP-13 inhibition, whereas MMP-13 inhibition did not increase anoikis in NG2-null cells, corroborating that retention of NG2 on the cell membrane is critical for sustaining anoikis, and its cleavage for mediating anoikis attenuation. Similarly, NG2 suppression with siRNA inhibited NG2 release and anoikis. In contrast, MMP-13 overexpression or exogenous MMP-13 reduced anoikis by more effectively shedding NG2. In conclusion, maintenance of NG2 on the cell surface promotes anoikis propagation, whereas its shedding by MMP-13 actions attenuates anoikis. Given that these findings are derived in the context of periodontal ligament fibroblasts, these data have implications for periodontal inflammation and periodontal disease pathogenesis.

show abstract

Section: Discussionsupporting

confidence: 54%

Shedding of NG2 by MMP-13 Attenuates Anoikis

Joo

Miao

Bermúdez

et al. 2014

DNA and Cell Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…MMP-2 production and activation is a major event in the pathogenesis of these diseases via its role in extracellular matrix destruction. The T. denticola dentilisin protease plays an important role in the up-regulation and activation of MMP-2 in PDL cells (Miao et al , 2011, Miao et al , 2014), thereby promoting further ECM destruction and release of fibronectin fragments, which have deleterious effects on the periodontal environment (Kapila et al , 1996, Kapila et al , 1999, Kapila et al , 2002, Jee et al , 2004, Dai et al , 2005, Tafolla et al , 2005, Ghosh et al , 2008, Joo et al , 2008, Joseph et al , 2010, Miao et al , 2011, Miao et al , 2014, Pereira et al , 2014). The oral spirochete T. lecithinolyticum is also reported to activate MMP-2, as are P. gingivalis and A. actinomycetemcomitans (Choi et al , 2001, Chang et al , 2002, Song et al , 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Destruction of the ECM in periodontitis results in the release of fibronectin (FN) fragments, which are considered markers of periodontal disease status (Huynh et al , 2002). Evidence from in vitro studies further indicate that these FN fragments, induce several detrimental effects, including induction of apoptosis and suppression of osteoblast differentiation of periodontal ligament cells (Kapila et al , 1996, Kapila et al , 1998, Kapila et al , 1999, Jee et al , 2004, Dai et al , 2005, Ghosh et al , 2008, Joseph et al , 2010), thereby further potentiating disease progression.…”

Section: Introductionmentioning

confidence: 99%

Treponema denticolaincreases MMP-2 expression and activation in the periodontium via reversible DNA and histone modifications

Ateia

Sutthiboonyapan

Kamarajan

et al. 2018

Cellular Microbiology

Self Cite

View full text Add to dashboard Cite

Host-derived matrix metalloproteinases (MMPs) and bacterial proteases mediate destruction of extracellular matrices and supporting alveolar bone in periodontitis. The Treponema denticola dentilisin protease induces MMP-2 expression and activation in periodontal ligament (PDL) cells, and dentilisin-mediated activation of pro-MMP-2 is required for cellular fibronectin degradation. Here, we report that T. denticola regulates MMP-2 expression through epigenetic modifications in the periodontium. PDL cells were treated with epigenetic enzyme inhibitors before or after T. denticola challenge. Fibronectin fragmentation, MMP-2 expression, and activation were assessed by immunoblot, zymography, and qRT-PCR, respectively. Chromatin modification enzyme expression in T. denticola-challenged PDL cells and periodontal tissues were evaluated using gene arrays. Several classes of epigenetic enzymes showed significant alterations in transcription in diseased tissue and T. denticola-challenged PDL cells. T. denticola-mediated MMP-2 expression and activation were significantly reduced in PDL cells treated with inhibitors of aurora kinases and histone deacetylases. In contrast, DNA methyltransferase inhibitors had little effect, and inhibitors of histone acetyltransferases, methyltransferases, and demethylases exacerbated T. denticola-mediated MMP-2 expression and activation. Chronic epigenetic changes in periodontal tissues mediated by T. denticola or other oral microbes may contribute to the limited success of conventional treatment of chronic periodontitis and may be amenable to therapeutic reversal.

show abstract

“…Depolymerized HA promotes angiogenesis and activates matrix metalloproteinases (MMPs) in a number of cell types and is proinflammatory [30][31][32][33][34][35][36][37][38][39][40]. Collagen [41] and fibronectin [42][43][44][45][46][47][48] breakdown products also upregulate production of active MMPs in a number of cell types. Thus, an imbalance in these components could lead to deleterious effects through excessive enzymatic degradation of matrix components in the developing joint.…”

Section: Isolated Cells In the Avascular Mid-and Inner 14-mentioning

confidence: 99%

Immunolocalization of lymphatic vessels in human fetal knee joint tissues

Melrose

Little

2010

Connective Tissue Research

View full text Add to dashboard Cite

We immunolocalized lymphatic and vascular blood vessels in 12- and 14-week-old human fetal knee joint tissues using a polyclonal antibody to a lymphatic vascular endothelium specific hyaluronan receptor (LYVE-1) and a monoclonal antibody to podoplanin (mAb D2-40). A number of lymphatic vessels were identified in the stratified connective tissues surrounding the cartilaginous knee joint femoral and tibial rudiments. These tissues also contained small vascular vessels with entrapped red blood cells which were imaged using Nomarsky DIC microscopy. Neither vascular nor lymphatic vessels were present in the knee joint cartilaginous rudiments. The menisci in 12-week-old fetal knees were incompletely demarcated from the adjacent tibial and femoral cartilaginous rudiments which was consistent with the ongoing joint cavitation process at the femoral-tibial junction. At 14 weeks of age the menisci were independent structural entities; they contained a major central blood vessel containing red blood cells and numerous communicating vessels at the base of the menisci but no lymphatic vessels. In contrast to the 12-week-old menisci, the 14-week meniscal rudiments contained abundant CD-31 and CD-34 positive but no lymphatic vessels. Isolated 14-week-old meniscal cells also were stained with the CD-31 and CD 34 antibodies; CD-68 +ve cells, also abundant in the 14-week-old menisci, were detectable to a far lesser degree in the 12-week menisci and were totally absent from the femoral and tibial rudiments. The distribution of lymphatic vessels and tissue macrophages in the fetal joint tissues was consistent with their roles in the clearance of metabolic waste and extracellular matrix breakdown products arising from the rapidly remodelling knee joint tissues.

show abstract

Specific Pro‐Apoptotic Fibronectin Fragments Modulate Proteinase Expression in Periodontal Ligament Cells

Abstract: These findings suggest that matrix-degrading proteinases may be involved in apoptosis as part of a unique mechanism of periodontal tissue breakdown, in which novel proteinases may help execute the dissolution of the extracellular matrix.

Cited by 10 publications

References 25 publications

Shedding of NG2 by MMP-13 Attenuates Anoikis

Shedding of NG2 by MMP-13 Attenuates Anoikis

Treponema denticolaincreases MMP-2 expression and activation in the periodontium via reversible DNA and histone modifications

Immunolocalization of lymphatic vessels in human fetal knee joint tissues

Contact Info

Product

Resources

About