Role of interleukin‐1 and tumor necrosis factor α in matrix degradation of human osteoarthritic cartilage

Kobayashi, Masahiko; Squires, Ginette R.; Mousa, Aisha; Tänzer, Michael; Zukor, David J.; Antoniou, John; Feige, Ulrich; Poole, A R

doi:10.1002/art.20776

Cited by 449 publications

(356 citation statements)

References 39 publications

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“…This finding has been previously reported in a human chondrocytic cell-line [64] and primary canine chondrocytes [77], whilst in vivo these changes lead to destruction of cartilage [78]. M a n u s c r i p t…”

Section: -Mshsupporting

confidence: 82%

Melanocortin peptides protect chondrocytes from mechanically induced cartilage injury

Kaneva

Kerrigan

Grieco

et al. 2014

Biochemical Pharmacology

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Conclusion:Melanocortin peptide pre-treatment prevented chondrocyte death following mechanical impact to cartilage and led to a marked reduction of pro-inflammatory cytokines, whilst prompting the production of anti-inflammatory/pro-resolving cytokine IL-10.Development of small molecule agonists towards melanocortin receptors could thus be a viable approach for preventing chondrocyte inflammation and death within cartilage and represent an alternative approach for the treatment of osteoarthritis.

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Section: -Mshsupporting

confidence: 82%

Melanocortin peptides protect chondrocytes from mechanically induced cartilage injury

Kaneva

Kerrigan

Grieco

et al. 2014

Biochemical Pharmacology

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“…Therefore, SW-1353 cells were treated with 50 nM LG268 for 24 hours in serumfree medium, followed by the addition of TNF␣ for another 24 hours. As expected (26), mRNA levels of MMP-1 and MMP-13 greatly increased with TNF␣ treatment, while pretreatment with LG268 significantly inhibited this induction (P ϭ 0.01 and P ϭ 0.004 respectively) ( Figure 3A).…”

Section: Specific Inhibition Of Mmp-1 and Mmp-13 Production By Pretresupporting

confidence: 78%

Regulation of matrix metalloproteinase gene expression by a retinoid X receptor–specific ligand

Burrage¹,

Huntington²,

Sporn³

et al. 2007

Arthritis & Rheumatism

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Objective. To evaluate the effects of LG100268 (LG268), a synthetic ligand for the nuclear hormone receptor retinoid X receptor, on the expression of matrix metalloproteinase 1 (MMP-1) and MMP-13 induced by proinflammatory cytokines in a chondrocyte model.Methods. SW-1353 human chondrosarcoma cells were used to study the effects of LG268 on interleukin-1␤ (IL-1␤)-stimulated MMP production and collagen degradation. Gene expression was determined by quantitative real-time reverse transcriptionpolymerase chain reaction, and protein levels were determined by Western blot analysis. Collagen degradation was determined by an in vitro matrix destruction assay. The effects of LG268 on nuclear protein binding and histone acetylation were determined by electrophoretic mobility shift assay and chromatin immunoprecipitation assay, respectively.Results.LG268 treatment specifically antagonized the IL-1␤-mediated induction of MMP-1 and MMP-13 heterogeneous nuclear RNA, messenger RNA, and protein. The inhibitory effect of LG268 was found to be due to a decrease in the rate of MMP-1 and MMP-13 transcription.LG268 treatment also prevented the in vitro degradation of a type I collagen matrix by IL-1␤-treated SW-1353 cells. The inhibitory effect of LG268 on MMP-1 and MMP-13 transcription appears to be mediated, at least in part, through modulation of histone modification in regions of the MMP-1 and MMP-13 promoters that contain binding sites for activator protein 1 transcription factors.Conclusion. These data indicate that LG268 treatment selectively inhibits inflammatory cytokineinduced production of MMP-1 and MMP-13 at the level of gene transcription and blocks collagen destruction by proinflammatory cytokine-stimulated chondrocytic cells. This study is among the first to describe how rexinoids affect gene expression, and the findings suggest that the rexinoid class of compounds may have a future role in preventing the irreversible collagen destruction seen in the arthritides.The destruction of joint tissues that is a hallmark of rheumatoid arthritis (RA) and osteoarthritis (OA) is mediated largely by members of the matrix metalloproteinase (MMP) family of enzymes (1-3). At low expression levels, these zinc-dependent endopeptidases maintain connective tissue homeostasis in a wide range of biologic functions (4). However, abnormally high levels of MMP expression have been linked to multiple pathologic states, including tumor invasion, atherosclerosis, and the arthritides (4). In humans, the MMP family currently encompasses 23 unique members, which degrade all constituents of the extracellular matrix (ECM) (5). The MMPs can be subdivided into 6 main classes (1,4,5), consisting of the collagenases (MMPs 1, 8, and 13), the gelatinases (MMPs 2 and 9), the stromelysins (MMPs 3, 10, and 11), the matrilysins (MMPs 7 and 26), the membrane-type MMPs (MMPs 14,15,16,17,24,and 25), and a diverse subgroup.The collagenase subgroup is unique in its ability to cleave fibrillar collagens, and their enzymatic activity represents a rate-limiting step...

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“…Activation of PARs is closely regulated by EPCR and TM, increased concentrations of which favor endogenous protein C activation by TM-bound thrombin and subsequent proteolysis of PARs and other substrates by APC (44). We found that chondrocyte expression of EPCR and TM was induced by IL-1␣ and TNF␣, both of which are implicated in cartilage degradation in OA (45). A critical role of EPCR and PAR activation in the effects of APC has been demonstrated in keratinocytes (46), and it will be important to determine if similar pathways are active in chondrocytes.…”

Section: Discussionmentioning

confidence: 74%

Activation of cartilage matrix metalloproteinases by activated protein C

Jackson

Smith

et al. 2009

Arthritis & Rheumatism

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Objective. To investigate the role of activated protein C (APC) in cartilage degradation.Methods. Chondrocyte expression of protein C, endothelial protein C receptor (EPCR), and thrombomodulin (TM) were evaluated by reverse transcriptionpolymerase chain reaction (RT-PCR). APC was immunolocalized in developing joints and in osteoarthritic (OA) cartilage from humans. The effect of APC on aggrecan and collagen degradation was examined in explant cultures of ovine cartilage in control cultures and in cultures stimulated with interleukin-1␣ (IL-1␣), tumor necrosis factor ␣ (TNF␣), or retinoic acid (RetA), using colorimetric assays and Western blotting. Chondrocyte expression of matrix metalloproteinases (MMPs), ADAMTS, and tissue inhibitor of metalloproteinases (TIMPs) was measured by RT-PCR. MMP-2 and MMP-9 activity was evaluated by gelatin zymography and MMP-13 by fluorogenic assay.Results. Positive cellular immunostaining for APC was found at sites of MMP activity in developing joints and in OA, but not normal, cartilage. Chondrocytes expressed messenger RNA for protein C, EPCR, and TM, with the latter 2 levels increased by IL-1␣ and TNF␣ stimulation. APC augmented aggrecan release and initiated collagen breakdown in IL-1␣-treated and TNF␣-treated cartilage, but not in normal or in RetAtreated cartilage. APC-stimulated aggrecan and collagen breakdown were due to MMP activity but were not associated with modulation of MMP, ADAMTS, or TIMP expression. APC resulted in MMP-13 activation in cartilage cultures. APC could not directly activate proMMP-13, but it was associated with increased MMP-2 and MMP-9 activity.Conclusion. APC may be a relevant activator of MMPs in cartilage and may play a role in progressive cartilage degradation in arthritis.

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Role of interleukin‐1 and tumor necrosis factor α in matrix degradation of human osteoarthritic cartilage

Cited by 449 publications

References 39 publications

Melanocortin peptides protect chondrocytes from mechanically induced cartilage injury

Melanocortin peptides protect chondrocytes from mechanically induced cartilage injury

Regulation of matrix metalloproteinase gene expression by a retinoid X receptor–specific ligand

Activation of cartilage matrix metalloproteinases by activated protein C

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