Attachment to laminin-111 facilitates transforming growth factor  -induced expression of matrix metalloproteinase-3 in synovial fibroblasts

Hoberg, Maik; Rudert, Maximilian; Pap, Thomas; Klein, Gerd; Aicher, Wilhelm K.

doi:10.1136/ard.2006.060228

Cited by 19 publications

(27 citation statements)

References 46 publications

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“…Moreover, in MSC attached to LM-111, TGF-β1 induced significant elevations in the expression of MMP-3 (5.7-fold, p<0.05), MMP-10 (20.4-fold, p<0.05) and MMP-13 (80.5-fold, p<0.05; Figure 2, Table 1). But in contrast to our results on synovial fibroblasts [1,2], attachment of MSC to Col-1 or LM-111 did not elevate the TGF-β1-activated expression of MMP-3 or MMP-10 beyond the expression levels recorded in TGF-β1 stimulated MSC grown in TCPS flasks (Figure 2A, 2C, 2E). …”

Section: Attachment To Extracellular Matrix Proteins Affects the Exprcontrasting

confidence: 56%

“…By aid of activation-specific antibodies and by use of specific inhibitors, we could prove that in MSC the expression of MMP-3 is elevated by TGF-β1 via all three pathways, Smad2, ERK1/2 and p38MAPK. This has also been seen in synovial fibroblasts [1,2]. Thus, the expression of MMP-10 is regulated mainly by Smad2 and ERK1/2 in MSC, and expression of MMP-13 is regulated in TGF-β1 activated MSC foremost via p38MAPK.…”

Section: Discussionmentioning

confidence: 72%

“…In contrast to MSC, attachment of synovial fibroblasts to LM-111 modulated the expression of MMP-3 and MMP-10, and the TGF-β1 induced expression of MMP-3 and MMP-10 was even enhanced in fibroblasts [1,2]. Activation of osteoblasts by TGF-β1 also activated the expression of MMP-3 and MMP-10.…”

Section: Discussionmentioning

confidence: 95%

“…We recently showed that TGF-β1 cooperates with integrin signalling upon attachment of synovial fibroblasts to LM-111, significantly boosting the expression of MMP-3 and MMP-10 [1,2]. Crosstalk between TGF-β and the integrin signalling pathway has been reported in epithelial cells as well [30].…”

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confidence: 99%

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The TGF-β1-Induced Expression of Matrix Metalloproteinases in Mesenchymal Stromal Cells is Influenced by Type of Substrate

Warstat

Felka²,

Mittag³

et al. 2011

J Tissue Sci Eng

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Section: Attachment To Extracellular Matrix Proteins Affects the Exprcontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

See 2 more Smart Citations

The TGF-β1-Induced Expression of Matrix Metalloproteinases in Mesenchymal Stromal Cells is Influenced by Type of Substrate

Warstat

Felka²,

Mittag³

et al. 2011

J Tissue Sci Eng

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“…594) of transcript variant 2 (product 311 bp, NM_001040021) to specifically amplify mature transcripts only. Commercially available PCR primers (Search LC Heidelberg, FRG) were employed for all other genes as well as for the controls (23). Amounts of target cDNA were normalized to GAPDH and to serial dilutions of recombinant controls in each PCR (5DDct method) (24).…”

Section: Enumeration Of Transcripts By Quantitative Polymerase Chain mentioning

confidence: 99%

Human mesenchymal stromal cells express CD14 cross‐reactive epitopes

et al. 2011

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Mesenchymal stromal cells (MSCs) do not express a unique definite epitope or marker gene. As such, minimal criteria were recently established for defining multipotent MSC. These criteria include expression of CD73, CD90, CD105, and a lack of hematopoietic marker expression. However, we detected binding of a CD14 antibody on bone marrowand placenta-derived MSC and investigated the staining of CD14 antibodies on these MSC in more detail. The MSC were isolated from human bone marrow and placenta tissue, expanded, characterized by quantitative RT-PCR, flow cytometry, and immunocytochemistry and differentiated to generate osteoblasts, chondrocytes, and adipocytes. The CD14-cross-reactive MSCs were enriched by cell sorting. Human peripheral blood mononuclear cells, fibroblasts, and hematopoietic cell lines served as controls. Utilizing four different clones of CD14 monoclonal antibodies, we found that three CD14 reagents stained the MSC. Two CD14 antibodies (HCD14 and M5E2) clearly marked the CD90 1 MSC population with distinct intensities, clone 134 620 generated a shift in flow cytometry histograms, but clone MFP9 did not stain MSC. Transcripts encoding CD14 or the CD14 protein were not detected in MSC. We confirm that bone marrow-and placentaderived MSC do not express CD14 and that the CD14 antibody MFP9 discriminates between monocytes and MSC more efficiently than the other antibodies employed here. This investigation does not contradict previous work but provides a more accurate characterization of MSC. ' 2011 International Society for Advancement of Cytometry

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The loss of α2β1 integrin suppresses joint inflammation and cartilage destruction in mouse models of rheumatoid arthritis

Peters

Wendholt

Strietholt

et al. 2012

Arthritis & Rheumatism

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Objective. Integrin ␣2␤1 functions as a major receptor for type I collagen on different cell types, including fibroblasts and inflammatory cells. Although in vitro data suggest a role for ␣2␤1 integrin in regulating both cell attachment and expression of matrixdegrading enzymes such as matrix metalloproteinases (MMPs), mice that lack the ␣2 integrin subunit (Itga2 ؊/؊ mice) develop normally and are fertile. We undertook this study to investigate the effect of Itga2 deficiency in 2 different mouse models of destructive arthritis: the antigen-induced arthritis (AIA) mouse model and the human tumor necrosis factor ␣ (TNF␣)-transgenic mouse model.Methods. AIA was induced in the knee joints of Itga2 ؊/؊ mice and wild-type controls. Human TNFtransgenic mice were crossed with Itga2 ؊/؊ mice and were assessed clinically and histopathologically for signs of arthritis, inflammation, bone erosion, and cartilage damage. MMP expression, proliferation, fibroblast attachment, and ERK activation were determined.Results. Under arthritic conditions, Itga2 deficiency led to decreased severity of joint pathology. Specifically, Itga2 ؊/؊ mice showed less severe clinical symptoms and dramatically reduced pannus formation and cartilage erosion. Mice lacking ␣2␤1 integrin exhibited reduced MMP-3 expression, both in their sera and in fibroblast-like synoviocytes (FLS), due to impaired ERK activation. Further, both the proliferation and attachment of FLS to cartilage were partially dependent on ␣2␤1 integrin in vitro and in vivo.Conclusion. Our findings suggest that ␣2␤1 integrin contributes significantly to inflammatory cartilage destruction by promoting fibroblast proliferation and attachment and MMP expression.

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Attachment to laminin-111 facilitates transforming growth factor -induced expression of matrix metalloproteinase-3 in synovial fibroblasts

Cited by 19 publications

References 46 publications

The TGF-β1-Induced Expression of Matrix Metalloproteinases in Mesenchymal Stromal Cells is Influenced by Type of Substrate

The TGF-β1-Induced Expression of Matrix Metalloproteinases in Mesenchymal Stromal Cells is Influenced by Type of Substrate

Human mesenchymal stromal cells express CD14 cross‐reactive epitopes

The loss of α2β1 integrin suppresses joint inflammation and cartilage destruction in mouse models of rheumatoid arthritis

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