Relationship between cartilage oligomeric matrix protein (COMP) and rheumatoid arthritis severity

Saghafi, Massoud; Khodashahi, Mandana; Saadati, Nayyereh; Azarian, Amir Abbas; Rezaieyazdi, Zahra; Salehi, Maryam; Sahebari, Maryam

doi:10.19082/5940

Cited by 12 publications

(11 citation statements)

References 28 publications

(36 reference statements)

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“… 28 The s COMP level also has the potential to be used as a biological marker for differentiating between patients with rheumatoid arthritis (RA) and healthy individuals. 29 , 30 The relevance of COMP and bone development or disease has been identified by previous studies. 31 , 32 Based on our study results, it is necessary to further explore the potential of COMP in the diagnosis and treatment of KBD.…”

Section: Discussionmentioning

confidence: 90%

The molecular mechanism study of COMP involved in the articular cartilage damage of Kashin-Beck disease

Liang

Wang

et al. 2020

Bone & Joint Research

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Aims Kashin-Beck disease (KBD) is a kind of chronic osteochondropathy, thought to be caused by environmental risk factors such as T-2 toxin. However, the exact aetiology of KBD remains unclear. In this study, we explored the functional relevance and biological mechanism of cartilage oligosaccharide matrix protein (COMP) in the articular cartilage damage of KBD. Methods The articular cartilage specimens were collected from five KBD patients and five control subjects for cell culture. The messenger RNA (mRNA) and protein expression levels were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot. The survival rate of C28/I2 chondrocyte cell line was detected by MTT assay after T-2 toxin intervention. The cell viability and mRNA expression levels of apoptosis related genes between COMP-overexpression groups and control groups were examined after cell transfection. Results The mRNA and protein expression levels of COMP were significantly lower in KBD chondrocytes than control chondrocytes. After the T-2 toxin intervention, the COMP mRNA expression of C28/I2 chondrocyte reduced and the protein level of COMP in three intervention groups was significantly lower than in the control group. MTT assay showed that the survival rate of COMP overexpression KBD chondrocytes were notably higher than in the blank control group. The mRNA expression levels of Survivin, SOX9, Caspase-3, and type II collagen were also significantly different among COMP overexpression, negative control, and blank control groups. Conclusion Our study results confirmed the functional relevance of COMP with KBD. COMP may play an important role in the excessive chondrocytes apoptosis of KBD patients. Cite this article: Bone Joint Res 2020;9(9):578–586.

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Section: Discussionmentioning

confidence: 90%

The molecular mechanism study of COMP involved in the articular cartilage damage of Kashin-Beck disease

Liang

Wang

et al. 2020

Bone & Joint Research

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“…Globally, most studies have shown that serum COMP level is higher in RA patients [13,14] . Consistent with these studies, our data also showed elevated COMP protein level in RA patients compared to normal controls.…”

Section: Discussionmentioning

confidence: 99%

Systemic Proteomic Analysis Reveals Distinct Exosomal Proteins Profiles in Rheumatoid Arthritis

Qin¹,

Song²,

Du³

et al. 2020

Preprint

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BackgroundRheumatoid arthritis (RA) is a heterogeneous and complex disease characterized by autoantibodies production and inflammation of the synovium. Its underlying mechanisms remain elusive. In recent years, exosomes have emerged as non-invasive biomarkers in diverse diseases. Due to its various inflammatory and immunological functions, some studies highlighted abnormalities of exosomes in RA, but fewer have paid attention to the broad spectrum of potential systemic markers of RA. The aim of this study was to identify exosomal candidate proteins in the pathogenesis of RA using systemic proteomic method. MethodsTotally 12 specimens of plasma from 6 RA patients and 6 age-and gender-matched controls from the Chinese population were obtained for nanoscale liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS) analysis to identify differentially expressed proteins (DEPs) in exosomes. Gene ontology (GO), protein interaction network (PPI) and KEGG pathway analyses were used in subcellular localization analysis. ResultsA total of 278 exosomal proteins were detected. Among them, 32 proteins were significantly upregulated (FC≥2.0 and P<0.05) and 5 proteins were downregulated (FC≤0.5 and P<0.05). Most of these DEPs were immunoglobullins (Igs). Bioinformatics analysis indicated that these Igs are involved in inflammatory response of RA through diverse immune regulatory pathways, such as NF-kappa B signaling pathway. PPI analysis revealed that transthyretin (TTR, P02766), angiotensinogen (AGT, P01019), lipopolysaccharide-binding protein (LBP, P18428), monocyte differentiation antigen CD14 (CD14, P08571), cartilage oligomeric matrix protein (COMP, P49747), serum amyloid P (SAP/APCS, P02743) and tenascin (TNC, P24821) can interact with each other or may form a regulatory networks. Subsequently, these cross-linked proteins may mainly involve in the NF-kappa B signaling pathway or inflammatory-related pathways to mediate the onset of RA. Noteworthy, among these exosomal DEPs, the complex composed of LBP and CD14 is involved in NF-kappa B signaling pathway, resulting in promoted expression of IL-8, TNF-α, and eventually leading to the development of RA.ConclusionsOur findings suggest distinct plasmic exosomal protein profiles in RA patients. These proteins not only take important parts in the vicious circle in the pathogenic process of RA, but also serve as novel biomarkers in RA diagnosis and prognosis.

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“…In patients with OA, these fragments are ~110 kDa in size, similar to the peptides generated by in vitro digestion of COMP with ADAMTS7 and 12 66 . Gene expression of both of these ADAMTS proteases is also elevated in the cartilage and synovium of patients with rheumatoid arthritis, where COMP levels are correlated positively with disease severity and negatively with cartilage thickness 18,69 …”

Section: Adamts Protease and Their Substrates In Musculoskeletal Devementioning

confidence: 95%

“…66 Gene expression of both of these ADAMTS proteases is also elevated in the cartilage and synovium of patients with rheumatoid arthritis, where COMP levels are correlated positively with disease severity and negatively with cartilage thickness. 18,69 The function of the COMP-degrading proteases in musculoskeletal development extends beyond their indications in arthritis. ADAMTS7 and 12 may regulate tendon development and prevent premature aging, coexpressed to preserve tendon cell identity.…”

Section: Comp-degrading Proteasesmentioning

confidence: 99%

The quest for substrates and binding partners: A critical barrier for understanding the role of ADAMTS proteases in musculoskeletal development and disease

Satz-Jacobowitz

Hubmacher

2020

Developmental Dynamics

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Secreted ADAMTS metalloproteases are involved in the sculpting, remodeling, and erosion of connective tissues throughout the body, including in the musculoskeletal system. ADAMTS proteases contribute to musculoskeletal development, pathological tissue destruction, and are mutated in congenital musculoskeletal disorders. Examples include versican cleavage by ADAMTS9 which is required for interdigital web regression during limb development, ADAMTS5-mediated aggrecan degradation in osteoarthritis resulting in joint erosion, and mutations in ADAMTS10 or ADAMTS17 that cause Weill-Marchesani syndrome, a short stature syndrome with bone, joint, muscle, cardiac, and eye involvement. Since the function of ADAMTS proteases and proteases in general is primarily defined by the molecular consequences of proteolysis of their respective substrates, it is paramount to identify all physiological substrates for each individual ADAMTS protease. Here, we review the current knowledge of ADAMTS proteases and their involvement in musculoskeletal development and disease, focusing on some of their known physiological substrates and the consequences of substrate cleavage. We further emphasize the critical need for the identification and validation of novel ADAMTS substrates and binding partners by describing the principles of mass spectrometry-based approaches and by emphasizing strategies that need to be considered for validating the physiological relevance for ADAMTS-mediated proteolysis of novel putative substrates.

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Relationship between cartilage oligomeric matrix protein (COMP) and rheumatoid arthritis severity

Cited by 12 publications

References 28 publications

The molecular mechanism study of COMP involved in the articular cartilage damage of Kashin-Beck disease

The molecular mechanism study of COMP involved in the articular cartilage damage of Kashin-Beck disease

Systemic Proteomic Analysis Reveals Distinct Exosomal Proteins Profiles in Rheumatoid Arthritis

The quest for substrates and binding partners: A critical barrier for understanding the role of ADAMTS proteases in musculoskeletal development and disease

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