The matrilin-3 VWA1 domain modulates interleukin-6 release from primary human chondrocytes

Klatt, Andreas R.; Paul-Klausch, Brigitte; Klinger, Gabriele; Hillebrand, U.; Kuhn, G.; Kobbe, Birgit; Renno, Joerg H.; Johannis, Wibke; Paulsson, Mats; Wagener, Raimund

doi:10.1016/j.joca.2013.03.005

Cited by 9 publications

(7 citation statements)

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“…Matrilin-3 is present at low levels in the joint articular surface and its deposition is upregulated in cartilage and in the synovial fluid of patients with OA as a consequence of cartilage degradation [56][57][58][59][60]. Studies with recombinant MATN3 and human primary chondrocytes have revealed that MATN3 exhibits a context-dependent anabolic or catabolic function by influencing the expression of pro-inflammatory cytokines, ECM degradation enzymes, and ECM synthesis [59,[61][62][63] through the modulation of protein kinase B (AKT) [59], interleukin-6 [62], and interleukin-1 [63,64] signaling pathways. The neoexpression of MATN1 was also observed in the cartilage of OA or rheumatoid arthritis patients [65,66], and MATN2 was recently observed in total knee arthroplasty and suggested as a biomarker for OA [67].…”

Section: Discussionmentioning

confidence: 99%

Mice Lacking the Matrilin Family of Extracellular Matrix Proteins Develop Mild Skeletal Abnormalities and Are Susceptible to Age-Associated Osteoarthritis

Fleischhauer

Nicolae

et al. 2020

IJMS

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Matrilins (MATN1, MATN2, MATN3 and MATN4) are adaptor proteins of the cartilage extracellular matrix (ECM), which bridge the collagen II and proteoglycan networks. In humans, dominant-negative mutations in MATN3 lead to various forms of mild chondrodysplasias. However, single or double matrilin knockout mice generated previously in our laboratory do not show an overt skeletal phenotype, suggesting compensation among the matrilin family members. The aim of our study was to establish a mouse line, which lacks all four matrilins and analyze the consequence of matrilin deficiency on endochondral bone formation and cartilage function. Matn1-4−/− mice were viable and fertile, and showed a lumbosacral transition phenotype characterized by the sacralization of the sixth lumbar vertebra. The development of the appendicular skeleton, the structure of the growth plate, chondrocyte differentiation, proliferation, and survival were normal in mutant mice. Biochemical analysis of knee cartilage demonstrated moderate alterations in the extractability of the binding partners of matrilins in Matn1-4−/− mice. Atomic force microscopy (AFM) revealed comparable compressive stiffness but higher collagen fiber diameters in the growth plate cartilage of quadruple mutant compared to wild-type mice. Importantly, Matn1-4−/− mice developed more severe spontaneous osteoarthritis at the age of 18 months, which was accompanied by changes in the biomechanical properties of the articular cartilage. Interestingly, Matn4−/− mice also developed age-associated osteoarthritis suggesting a crucial role of MATN4 in maintaining the stability of the articular cartilage. Collectively, our data provide evidence that matrilins are important to protect articular cartilage from deterioration and are involved in the specification of the vertebral column.

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Section: Discussionmentioning

confidence: 99%

Mice Lacking the Matrilin Family of Extracellular Matrix Proteins Develop Mild Skeletal Abnormalities and Are Susceptible to Age-Associated Osteoarthritis

Fleischhauer

Nicolae

et al. 2020

IJMS

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“…Over the past few years, the extracellular matrix has raised more than just a rigid network for cellular attachment. In addition to their function as structural components, Matrilin-3 and Cyclin-I play an important role in cartilage maintenance by improving tissue engineering strategies and targeting the tissue repair (4,16). However, with unknown etiology, TD has been attributed to abnormal chondrocytic differentiation, changes in the activities of matrix metalloproteinase, and changes in genes encoding vascular endothelial growth factor (VEGF) signaling pathways (2,3,20).…”

Section: Discussionmentioning

confidence: 99%

Expression of Genes Encoding Matrilin-3 and Cyclin-I During the Impairment and Recovery of Chicken Growth Plate in Tibial Dyschondroplasia

et al. 2014

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Tibial dyschondroplasia (TD) is a skeletal disease characterized by the disruption ofendochondral bone formation in avian species. The aim of this study was to determine the expression of Matrilin-3 and Cyclin-I genes in chicken growth plate during impairment and recovery from TD. Gene expressions were analyzed by polymerase chain reaction, and proteins by immunohistochemistry and in situ hybridizations. Expression of genes encoding Matrilin-3 and Cyclin-I were diminished with parallel decrease in proteins during TD, with fewer signs of cartilage cell differentiation. In contrast, there was an increase in mRNA expressions and protein levels of both genes during the recovery phase. These findings suggest that the Matrilin-3 and Cyclin-I genes also play a role in chondrocyte differentiation during the impairment and recovery of growth plate in TD.

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“…It is hypothesized that elevated levels of matrilin-3 could in turn increase the expression of ADAMTS4 and ADAMTS5 via IL-1β [ 60 ]. In support of this, Klatt et al [ 61 ] showed that VWFA domains present in matrilin-3 are responsible for IL-6 expression in primary human chondrocytes (See Figure 2 ). Matrilin-3 function shifts from an anabolic to a catabolic effect on ECM components, possibly due to a change from a very low concentration range (100 to 200 ng/mL) to a supra-physiological range (5 to 50 μg/mL).…”

Section: Role Of Matrilin-3mentioning

confidence: 75%

Matrilin-3 Role in Cartilage Development and Osteoarthritis

Muttigi

Han

Park

et al. 2016

IJMS

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The extracellular matrix (ECM) of cartilage performs essential functions in differentiation and chondroprogenitor cell maintenance during development and regeneration. Here, we discuss the vital role of matrilin-3, an ECM protein involved in cartilage development and potential osteoarthritis pathomechanisms. As an adaptor protein, matrilin-3 binds to collagen IX to form a filamentous network around cells. Matrilin-3 is an essential component during cartilage development and ossification. In addition, it interacts directly or indirectly with transforming growth factor β (TGF-β), and bone morphogenetic protein 2 (BMP2) eventually regulates chondrocyte proliferation and hypertrophic differentiation. Interestingly, matrilin-3 increases interleukin receptor antagonists (IL-Ra) in chondrocytes, suggesting its role in the suppression of IL-1β-mediated inflammatory action. Matrilin-3 downregulates the expression of matrix-degrading enzymes, such as a disintegrin metalloproteinase with thrombospondin motifs 4 (ADAMTS4) and ADAMTS5, matrix metalloproteinase 13 (MMP13), and collagen X, a hypertrophy marker during development and inflammatory conditions. Matrilin-3 essentially enhances collagen II and aggrecan expression, which are required to maintain the tensile strength and elasticity of cartilage, respectively. Interestingly, despite these attributes, matrilin-3 induces osteoarthritis-associated markers in chondrocytes in a concentration-dependent manner. Existing data provide insights into the critical role of matrilin-3 in inflammation, matrix degradation, and matrix formation in cartilage development and osteoarthritis.

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The matrilin-3 VWA1 domain modulates interleukin-6 release from primary human chondrocytes

Cited by 9 publications

References 10 publications

Mice Lacking the Matrilin Family of Extracellular Matrix Proteins Develop Mild Skeletal Abnormalities and Are Susceptible to Age-Associated Osteoarthritis

Mice Lacking the Matrilin Family of Extracellular Matrix Proteins Develop Mild Skeletal Abnormalities and Are Susceptible to Age-Associated Osteoarthritis

Expression of Genes Encoding Matrilin-3 and Cyclin-I During the Impairment and Recovery of Chicken Growth Plate in Tibial Dyschondroplasia

Matrilin-3 Role in Cartilage Development and Osteoarthritis

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