Toll‐like receptors and chondrocytes: The lipopolysaccharide‐induced decrease in cartilage matrix synthesis is dependent on the presence of toll‐like receptor 4 and antagonized by bone morphogenetic protein 7

Bobacz, Klaus; Sunk, Ilse-Gerlinde; Hofstaetter, Jochen G.; Amoyo, L.; Toma, Cyril D.; Akira, Shizuo; Weichhart, Thomas; Säemann, Marcus D.; Smolen, Josef S

doi:10.1002/art.22637

Cited by 106 publications

(115 citation statements)

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“…A possible reason for these opposite function of BMP4 in regulating immune responses under different conditions may be due to the cross-talk between BMP family members and other signaling pathways [15], among them the TLR signaling that mediates innate or adaptive immune responses might be a top candidate [16][17][18][19][20]. The different pathophysiological environment might also contribute to the differential effects of BMP4 in cells from different location.…”

Section: Discussionmentioning

confidence: 99%

Bone morphogenetic protein 4 inhibits liposaccharide‐induced inflammation in the airway

Wang

et al. 2014

Eur J Immunol

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Bone morphogenetic protein 4 (BMP4) is a multifunctional growth factor that belongs to the TGF-β superfamily. The role of BMP4 in lung diseases is not fully understood. Here, we demonstrate that BMP4 was upregulated in lungs undergoing lipopolysaccharide (LPS)-induced inflammation, and in airway epithelial cells treated with LPS or TNF-α. BMP4 mutant (BMP4 Keywords: Airway inflammation r BMP4 r LPS r Lung function r Pseudomonas aeruginosaAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionInflammation is a complex response that can be both defensive and harmful to the body. Although the primary role of inflammaCorrespondence: Prof. Wenju Lu e-mail: wlu92@yahoo.com tion is to eliminate the detrimental factors in tissues, the out-ofcontrolled inflammatory responses will lead to tissue damage that is even more harmful than the primary disease condition. Establishment of inflammatory cascades includes the release of both * These authors contributed equally to this work.C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 3284 Zhengtu Li et al. Eur. J. Immunol. 2014. 44: 3283-3294 pro-and anti-inflammatory mediators and the maturation, activation, and migration of the responding inflammatory cells [1]. The excessive inflammation in the lung causes lung injury that includes reduced alveolar-capillary barrier function, increased pulmonary vascular permeability, leukocyte infiltration into the alveolar space, etc. [2]. If the inflammatory factors cannot be cleared out timely, it makes the acute inflammation turn into chronic condition [3]. Accumulating evidence indicates that transforming growth factor β (TGF-β) plays a determining role in regulating both innate and acquired immunity [4]. TGF-β1 null mice exhibit widespread lethal inflammation in tissue, primarily in the heart and lung [5]. In addition, TGF-β1 stimulates fibroblast proliferation, promoting airway remodeling during chronic lung inflammation associated with asthma and chronic obstructive pulmonary disease (COPD) [6]. Bone morphogenetic proteins (BMPs) are multifunctional growth factors that belong to TGF-β superfamily members [7]. Owing to their chemotactic activity on fibroblasts, myocytes, and inflammatory cells, BMPs were also considered to influence inflammatory processes in adults [8]. Bone morphogenetic protein 4 (BMP4), a member of the BMPs family, is primarily expressed in airway epithelial cells and plays a key role in the early stage of lung development [9]. BMP4 was demonstrated being upregulated in ovabumin-induced inflammation in mouse lung [8]. However, the role of BMP4 in lung inflammation, particularly in lung innate immunity is unknown.In this study, we hypothesized that BMP4 might participate in regulating the innate immune responses to bacterial infection. We examined the lung BMP4 expression during LPS-induced inflammation. Moreover, we compared the LPS-induced and Pseudomonas aeruginosa (PA) induced airway inflammation and pulmonary bacterial...

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Section: Discussionmentioning

confidence: 99%

Bone morphogenetic protein 4 inhibits liposaccharide‐induced inflammation in the airway

Wang

et al. 2014

Eur J Immunol

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“…A direct effect of TLR4 activation on chondrocyte anabolic function, eg, collagen type II and aggrecan synthesis, has been reported before. 1 In addition, TLR4 activation of primary osteoarthritic chondrocytes strongly induces MMP and NO release from these cells. 45 In vivo evidence supporting the contribution of TLR4 to MMP-mediated cartilage destruction comes from our previous findings indicating TLR4-dependent expression of the MMP-specific aggrecan neoepitope VDIPEN in murine arthritic joints.…”

Section: Tlr4mentioning

confidence: 99%

“…TLRs are a family of evolutionarily conserved transmembrane receptors, which are expressed by a variety of immune cells, including monocytes, macrophages, dendritic cells, neutrophils, B cells, and certain types of T cells; however, nonimmune cells such as fibroblasts and chondrocytes also express TLRs. 1,2 The major function of TLRs is to recognize pathogen-associated molecular patterns, which are highly conserved in evolution and are shared by many microorganisms. At the same time, TLRs show considerable target specificity.…”

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confidence: 99%

Local Interleukin-1-Driven Joint Pathology Is Dependent on Toll-Like Receptor 4 Activation

Abdollahi‐Roodsaz

Joosten

Koenders

et al. 2009

The American Journal of Pathology

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Toll-like receptors (TLRs) may contribute to the pathogenesis of chronic inflammatory destructive diseases through the recognition of endogenous ligands produced on either inflammation or degeneration of the extracellular matrix. The presence of endogenous TLR agonists has been reported in rheumatoid joints. In the present study, we investigated the significance of TLR2 and TLR4 activation by locallyproduced endogenous ligands in the severity of joint inflammation and destruction. Local joint pathology independent of systemic immune activation was induced by overexpression of interleukin (IL)-1 and TNF in naive joints using adenoviral gene transfer. Here, we report that at certain doses, IL-1-induced local joint inflammation, cartilage proteoglycan depletion, and bone erosion are dependent on TLR4 activation, whereas TLR2 activation is not significantly involved. In comparison, tumor necrosis factor ␣-driven joint pathology seemed to be less dependent on TLR2 and TLR4. The severity of IL-1-induced bone erosion and irreversible cartilage destruction was markedly reduced in TLR4 ؊/؊ mice, even though the degree of inflammation was similar, suggesting uncoupled processes. Furthermore, the expression of cathepsin K, a marker for osteoclast activity, induced by IL-1␤ was dependent on TLR4. Overexpression of IL-1␤ in the joint as well as ex vivo IL-1 stimulation of patellae provoked the release of endogenous TLR4 agonists capable of inducing TLR4-mediated cytokine production. These data emphasize the potential relevance of TLR4 activation in rheumatoid arthritis , particularly with respect to IL-1-mediated joint pathology.

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“…Therefore, application of LPS in our model should affect cartilage (Bobacz et al, 2007;Ichiseki et al, 2004a). Several studies have demonstrated that LPS activates many transcription factors and cytokines, including NF-B, IL-33 (Espinassous et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

A mouse model of osteonecrotic femoral head induced by methylprednisolone and liposaccharide

Le¹,

Phi²,

Dao³

et al. 2016

Biomed Res Ther

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Abstract-Introduction:Osteonecrosis of the femoral head is caused by various factors, including prolonged use of steroid drugs, use of alcohol, vascular injuries and hemoglobinopathies. This study aims to develop a mouse model for glucocorticoid-induced avascular necrosis (AVN) of the femoral head.Methods: Adult mice were randomly divided into two groups: experimental and control. Group A (the experimental group) was given (via intramuscular injection) 10 mg/kg of lipopolysaccharide (LPS) and 30 mg/kg of methylprednisolone (MPS). Each mouse additionally received MPS in divided oral doses of 13 mg/kg for 10 consecutive days. Group B (the control group) received normal saline at the same location and same volume as those in Group A. Histological changes of the femoral heads were observed by electron microscopy at 3, 5, and 7 weeks after the last chemical injection. The percentage of empty lacunae was measured randomly and the expression of fibrocartilage was evaluated using an image analyzing system. The expression of CD31 and VEGF-R2 were observed by immunohistochemistry. The bone marrow-derived mononuclear cells were stained with propidium iodide and cell cycle was analyzed by flow cytometry. Results:The results showed that at weeks 3 and 5, mice in Group A showed an increase in body weight. From weeks 5 to 7, mouse body weight in both groups remained constant. No difference in bone morphology was observed at week 7. The percentage of empty lacunae was 5.87 2.49% at week 5 and 21.58 8.10% at week 7. After 7 weeks, chondrocyte degeneration and fibrocartilage expression were observed. Moreover, the density of CD31 and VEGF-R2 markers increased in the femoral head. The rate of apoptosis in the bone marrow increased at week 3 then decreased. Conclusion: The data show that MPS, combined with LPS, can induce in mice features typical of early AVN of the femoral head.

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Toll‐like receptors and chondrocytes: The lipopolysaccharide‐induced decrease in cartilage matrix synthesis is dependent on the presence of toll‐like receptor 4 and antagonized by bone morphogenetic protein 7

Cited by 106 publications

References 77 publications

Bone morphogenetic protein 4 inhibits liposaccharide‐induced inflammation in the airway

Bone morphogenetic protein 4 inhibits liposaccharide‐induced inflammation in the airway

Local Interleukin-1-Driven Joint Pathology Is Dependent on Toll-Like Receptor 4 Activation

A mouse model of osteonecrotic femoral head induced by methylprednisolone and liposaccharide

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