Combined role of type IX collagen and cartilage oligomeric matrix protein in cartilage matrix assembly: Cartilage oligomeric matrix protein counteracts type IX collagen–induced limitation of cartilage collagen fibril growth in mouse chondrocyte cultures

Blumbach, Katrin; Bastiaansen-Jenniskens, Y.M.; DeGroot, Jeroen; Paulsson, Mats; Osch, Gerjo J.V.M. van; Zaucke, Frank

doi:10.1002/art.24979

Cited by 44 publications

(27 citation statements)

References 42 publications

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“…As a structural component of nucleus pulposus and annulus fibrosus of intervertebral disc, collagen IX acts as a bridge between collagens and non-collagenous proteins in tissues, which is essential to the proper formation of the collagen type II/IX/XI heteropolymer (Wu and Eyre, 1984;Koelling et al, 2008;Huang et al, 2009;Blumbach et al, 2009;Zhu et al, 2011). Type IX collagen is composed of 3 genetically distinct α polypeptide chains, i.e., α1(IX), α2(IX), and α3(IX), which are encoded by COL9A1, COL9A2, and COL9A3, respectively.…”

Section: Introductionmentioning

confidence: 99%

The role of smoking status and collagen IX polymorphisms in the susceptibility to cervical spondylotic myelopathy

Wang

Shi²,

Chen³

et al. 2012

Genet. Mol. Res.

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ABSTRACT.We investigated a possible association of collagen IX tryptophan (Trp) alleles (Trp2 and Trp3) and smoking with cervical spondylotic myelopathy (CSM) in 172 Chinese patients and 176 age-and gender-matched controls. The smoking status was evaluated by smoking index (SI). The CSM cases had a significantly higher prevalence of Trp2 alleles (Trp2+) than controls (19.8 vs 6.2%, P = 0.002), but the prevalence of Trp3 alleles (Trp3+) was similar between the two groups (23.3 vs 21.6%, P = 0.713). Logistic regression analyses showed that the subjects with Trp2+ had a higher risk for CSM. We thus analyzed whether smoking status influenced the association between Trp2 alleles and CSM risk. Among Trp2+ subjects with an SI less than 100, the smoking status did not influence the effect of risk for SCM [odds ratio (OR) = 1.34, 95% confidential interval (95%CI) = 0.85-2.18, P > 0.05]. When SI increased from 101 to 300, the OR for CSM reached 3.34 (95%CI = 2.11-5.67, P = 0.011); when SI was more than 300, the OR for CSM reached 5.56 (95%CI = 3.62-7.36, P < 0.001). Among Trp2- Association of smoking and collagem IX with CSM subjects with SI more than 300, the OR for CSM increased 2.14 (95%CI = 1.15-4.07, P = 0.024). We found a significant association between the Trp2 alleles and CSM risk and smoking amplifies this risk, suggesting that smoking abstinence is important for reducing CSM occurrence in subjects with high genetic risk.

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Section: Introductionmentioning

confidence: 99%

The role of smoking status and collagen IX polymorphisms in the susceptibility to cervical spondylotic myelopathy

Wang

Shi²,

Chen³

et al. 2012

Genet. Mol. Res.

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“…The pentameric COMP is proposed to function as a linker protein between collagen and other extracellular matrix molecules that regulate collagen fibrilogenesis 6–9 . COMP knock-out mice are phenotypically normal 10 , suggesting that COMP’s function might be compensated by other members of the TSP family or other extracellular matrix constituents.…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis with collagen type II distinguishes cartilage oligomeric matrix protein as a primary TGFβ-responsive gene

Haudenschild

Posey³

et al. 2011

Osteoarthritis and Cartilage

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Summary Objective This study aims to investigate the regulation of expression of Cartilage oligomeric matrix protein (COMP), which is predominately expressed by chondrocytes and functions to organize the extracellular matrix. Mutations in COMP cause two skeletal dysplasias: pseudoachondroplasia and multiple epiphyseal dysplasia. The mechanism controlling COMP expression during chondrocyte differentiation is still poorly understood. Design Primary human bone marrow-derived stem cells were induced to differentiate into chondrocyte by pellet cultures. We then compared the temporal expression of COMP with the well-characterized cartilage-specific Type II collagen (Col2a1), and their response to transforming growth factor (TGF) β and Sox trio (Sox5, 6, and 9) stimulation. Results COMP and Col2a1 expression are differentially regulated by three distinct mechanisms. First, upregulation of COMP mRNA precedes Col2a1 by several days during chondrogenesis. Second, COMP expression is independent of high cell density but requires TGF-β1. Induction of COMP mRNA by TGF-β1 is detected within 2 h in the absence of protein synthesis and is blocked by specific inhibitors of the TGFβ signaling pathway; and therefore, COMP is a primary TFGβ-response gene. Lastly, while Col2a1 expression is intimately controlled by the Sox trio, overexpression of Sox trio fails to activate the COMP promoter. Conclusion COMP and Col2a1 expression are regulated differently during chondrogenesis. COMP is a primary response gene of TGFβ and its fast induction during chondrogenesis suggests that COMP is suitable for rapidly accessing the chondrogenic potential of stem cells.

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“…MED is genetically heterogeneous, and autosomal‐dominant forms of the disease arise from mutations in the genes encoding matrilin 3, cartilage oligomeric matrix protein (COMP), and type IX collagen (3–5). Although present in other musculoskeletal tissues, matrilin 3, COMP, and type IX collagen are expressed primarily by chondrocytes and have been shown to interact with each other, both in vitro and in vivo (6–13).…”

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Loss of matrilin 1 does not exacerbate the skeletal phenotype in a mouse model of multiple epiphyseal dysplasia caused by a Matn3 V194D mutation

Bell

Piróg

Fresquet

et al. 2012

Arthritis & Rheumatism

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ObjectiveMutations in matrilin 3 can result in multiple epiphyseal dysplasia (MED), a disease characterized by delayed and irregular bone growth and early-onset osteoarthritis. Although intracellular retention of the majority of mutant matrilin 3 was previously observed in a murine model of MED caused by a Matn3 V194D mutation, some mutant protein was secreted into the extracellular matrix. Thus, it was proposed that secretion of mutant matrilin 3 may be dependent on the formation of hetero-oligomers with matrilin 1. The aim of this study was to investigate the hypothesis that deletion of matrilin 1 would abolish the formation of matrilin 1/matrilin 3 hetero-oligomers, eliminate the secretion of mutant matrilin 3, and influence disease severity.MethodsMice with a Matn3 V194D mutation were crossed with Matn1-null mice, generating mice that were homozygous for V194D and null for matrilin 1. This novel mouse was used for in-depth phenotyping, while cartilage and chondrocytes were studied both histochemically and biochemically.ResultsEndochondral ossification was not disrupted any further in mice with a double V194D mutation compared with mice with a single mutation. A similar proportion of mutant matrilin 3 was present in the extracellular matrix, and the amount of retained mutant matrilin 3 was not noticeably increased. Retained mutant matrilin 3 formed disulfide-bonded aggregates and caused the co-retention of matrilin 1.ConclusionWe showed that secretion of matrilin 3 V194D mutant protein is not dependent on hetero-oligomerization with matrilin 1, and that the total ablation of matrilin 1 expression has no impact on disease severity in mice with MED. Mutant matrilin 3 oligomers form non-native disulfide-bonded aggregates through the misfolded A domain.

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Combined role of type IX collagen and cartilage oligomeric matrix protein in cartilage matrix assembly: Cartilage oligomeric matrix protein counteracts type IX collagen–induced limitation of cartilage collagen fibril growth in mouse chondrocyte cultures

Cited by 44 publications

References 42 publications

The role of smoking status and collagen IX polymorphisms in the susceptibility to cervical spondylotic myelopathy

The role of smoking status and collagen IX polymorphisms in the susceptibility to cervical spondylotic myelopathy

Comparative analysis with collagen type II distinguishes cartilage oligomeric matrix protein as a primary TGFβ-responsive gene

Loss of matrilin 1 does not exacerbate the skeletal phenotype in a mouse model of multiple epiphyseal dysplasia caused by a Matn3 V194D mutation

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