Dataset Information

Toll-like receptors in human chondrocytes and osteoarthritic cartilage.

ABSTRACT:

Background and purpose

Degenerating cartilage releases potential danger signals that react with Toll-like receptor (TLR) type danger receptors. We investigated the presence and regulation of TLR1, TLR2, and TLR9 in human chondrocytes.

Methods

We studied TLR1, TLR2, TLR4, and TLR9 mRNA (qRT-PCR) and receptor proteins (by immunostaining) in primary mature healthy chondrocytes, developing chondrocytes, and degenerated chondrocytes in osteoarthritis (OA) tissue sections of different OARSI grades. Effects of a danger signal and of a pro-inflammatory cytokine on TLRs were also studied.

Results

In primary 2D-chondrocytes, TLR1 and TLR2 were strongly expressed. Stimulation of 2D and 3D chondrocytes with a TLR1/2-specific danger signal increased expression of TLR1 mRNA 1.3- to 1.8-fold, TLR2 mRNA 2.6- to 2.8-fold, and TNF-? mRNA 4.5- to 9-fold. On the other hand, TNF-? increased TLR1 mRNA] expression 16-fold, TLR2 mRNA expression 143- to 201-fold, and TNF-? mRNA expression 131- to 265-fold. TLR4 and TLR9 mRNA expression was not upregulated. There was a correlation between worsening of OA and increased TLR immunostaining in the superficial and middle cartilage zones, while chondrocytes assumed a CD166(×) progenitor phenotype. Correspondingly, TLR expression was high soon after differentiation of mesenchymal stem cells to chondrocytes. With maturation, it declined (TLR2, TLR9).

Interpretation

Mature chondrocytes express TLR1 and TLR2 and may react to cartilage matrix/chondrocyte-derived danger signals or degradation products. This leads to synthesis of pro-inflammatory cytokines, which stimulate further TLR and cytokine expression, establishing a vicious circle. This suggests that OA can act as an autoinflammatory disease and links the old mechanical wear-and-tear concept with modern biochemical views of OA. These findings suggest that the chondrocyte itself is the earliest and most important inflammatory cell in OA.

SUBMITTER: Sillat T

PROVIDER: S-EPMC3851674 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Publications

Toll-like receptors in human chondrocytes and osteoarthritic cartilage.

Sillat Tarvo T Barreto Gonçalo G Clarijs Paul P Soininen Antti A Ainola Mari M Pajarinen Jukka J Korhonen Matti M Konttinen Yrjö T YT Sakalyte Regina R Hukkanen Mika M Ylinen Pekka P Nordström Dan C E DC

Acta orthopaedica 20131118 6

<h4>Background and purpose</h4>Degenerating cartilage releases potential danger signals that react with Toll-like receptor (TLR) type danger receptors. We investigated the presence and regulation of TLR1, TLR2, and TLR9 in human chondrocytes.<h4>Methods</h4>We studied TLR1, TLR2, TLR4, and TLR9 mRNA (qRT-PCR) and receptor proteins (by immunostaining) in primary mature healthy chondrocytes, developing chondrocytes, and degenerated chondrocytes in osteoarthritis (OA) tissue sections of different O ...[more]

PMID: 24237425

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Dataset Information

Toll-like receptors in human chondrocytes and osteoarthritic cartilage.

Background and purpose

Methods

Results

Interpretation

Publications

Toll-like receptors in human chondrocytes and osteoarthritic cartilage.

Similar Datasets

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