scholarly journals Development of a Cartilage Oligomeric Matrix Protein Neo-Epitope Assay for the Detection of Intra-Thecal Tendon Disease

2020 ◽  
Vol 21 (6) ◽  
pp. 2155
Author(s):  
Roger Smith ◽  
Patrik Önnerfjord ◽  
Kristin Holmgren ◽  
Shacko di Grado ◽  
Jayesh Dudhia
Keyword(s):  
Molecular Marker ◽  
Cartilage Oligomeric Matrix Protein ◽  
Matrix Protein ◽  
Competitive Inhibition ◽  
Objective Assessment ◽  
Clinical Signs ◽  
Tendon Injury ◽  
Cross Reactivity ◽  
Polyclonal Antiserum ◽  
Synovial Fluids

The diagnosis of tendon injury relies on clinical signs and diagnostic imaging but imaging is subjective and does not always correlate with clinical signs. A molecular marker would potentially offer a sensitive and specific diagnostic tool that could also provide objective assessment of healing for the comparison of different treatments. Cartilage Oligomeric Matrix Protein (COMP) has been used as a molecular marker for osteoarthritis in humans and horses but assays for the protein in tendon sheath synovial fluids have shown overlap between horses affected by tendinopathy and controls. We hypothesized that quantifying a COMP neoepitope would be more discriminatory of injury. COMP fragments were purified from synovial fluids of horses with intra-thecal tendon injuries and media from equine tendon explants, and mass spectrometry of a consistent and abundant fragment revealed a ~100 kDa COMP fragment with a new N-terminus at the 78th amino-acid (NH2-TPRVSVRP) located just outside the junctional region of the protein. A competitive inhibition ELISA based on a polyclonal antibody raised to this sequence yielded more than a 10-fold rise in the mean neoepitope levels for tendinopathy cases compared to controls (5.3 ± 1.3 µg/mL (n = 7) versus 58.8 ± 64.3 µg/mL (n = 13); p = 0.002). However, there was some cross-reactivity of the neoepitope polyclonal antiserum with intact COMP, which could be blocked by a peptide spanning the neoepitope. The modified assay demonstrated a lower concentration but a significant > 500-fold average rise with tendon injury (2.5 ± 2.2 ng/mL (n = 6) versus 1029.8 ± 2188.8 ng/ml (n = 14); p = 0.013). This neo-epitope assay therefore offers a potentially useful marker for clinical use.

scholarly journals Cartilage Oligomeric Matrix Protein-Deficient Mice Have Normal Skeletal Development

2002 ◽  
Vol 22 (12) ◽  
pp. 4366-4371 ◽  
Author(s):  
Liz Svensson ◽  
Attila Aszódi ◽  
Dick Heinegård ◽  
Ernst B. Hunziker ◽  
Finn P. Reinholt ◽  
...  
Keyword(s):  
Cartilage Oligomeric Matrix Protein ◽  
Matrix Protein ◽  
Skeletal Development ◽  
Clinical Signs ◽  
Immunohistochemical Analysis ◽  
Epiphyseal Dysplasia ◽  
Comp Gene ◽  
Deficient Mice

ABSTRACT Cartilage oligomeric matrix protein (COMP) belongs to the thrombospondin family and is a homopentamer primarily expressed in cartilage. Mutations in the COMP gene result in the autosomal dominant chondrodysplasias pseudoachondroplasia (PSACH) and some types of multiple epiphyseal dysplasia (MED), which are characterized by mild to severe short-limb dwarfism and early-onset osteoarthritis. We have generated COMP-null mice to study the role of COMP in vivo. These mice show no anatomical, histological, or ultrastructural abnormalities and show none of the clinical signs of PSACH or MED. Northern blot analysis and immunohistochemical analysis of cartilage indicate that the lack of COMP is not compensated for by any other member of the thrombospondin family. The results also show that the phenotype in PSACH/MED cartilage disorders is not caused by the reduced amount of COMP.

scholarly journals Analysis of cartilage oligomeric matrix protein (COMP) in synovial fibroblasts and synovial fluids

Rheumatology ◽  
1998 ◽  
Vol 37 (7) ◽  
pp. 721-728 ◽  
Author(s):  
K. M. Hummel ◽  
M. Neidhart ◽  
V. Vilim ◽  
N. Hauser ◽  
W. K. Aicher ◽  
...  
Keyword(s):  
Cartilage Oligomeric Matrix Protein ◽  
Matrix Protein ◽  
Synovial Fibroblasts ◽  
Synovial Fluids

scholarly journals Measurement of cartilage oligomeric matrix protein (COMP) in normal and diseased equine synovial fluids

2001 ◽  
Vol 9 (2) ◽  
pp. 119-127 ◽  
Author(s):  
K. Misumi ◽  
V. Vilim ◽  
P.D. Clegg ◽  
C.C.M. Thompson ◽  
S.D. Carter
Keyword(s):  
Cartilage Oligomeric Matrix Protein ◽  
Matrix Protein ◽  
Synovial Fluids

Can Tocilizumab Decrease Cartilage Oligomeric Matrix Protein Levels and Disease Activity in Patients with Long-Standing Rheumatoid Arthritis?

2015 ◽  
Vol 11 (999) ◽  
pp. 1-1
Author(s):  
Maurizio Benucci ◽  
Francesca Meacci ◽  
Mariangela Manfredi ◽  
Francesca Gobbi ◽  
Maria Infantino ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Cartilage Oligomeric Matrix Protein ◽  
Matrix Protein ◽  
Protein Levels

scholarly journals Analysis of Cartilage Oligomeric Matrix Protein (COMP) in Synovial Fluid, Serum and Urine from 51 Racehorses with Carpal Bone Fracture

2008 ◽  
Vol 70 (9) ◽  
pp. 915-921 ◽  
Author(s):  
Koh ARAI ◽  
Masaaki TAGAMI ◽  
Takashi HATAZOE ◽  
Eikoh NISHIMATSU ◽  
Yuri SHIMIZU ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Bone Fracture ◽  
Cartilage Oligomeric Matrix Protein ◽  
Matrix Protein ◽  
Carpal Bone ◽  
Serum And Urine

scholarly journals Cartilage oligomeric matrix protein is an endogenous β-arrestin-2-selective allosteric modulator of AT1 receptor counteracting vascular injury

Cell Research ◽  
2021 ◽  
Author(s):  
Yi Fu ◽  
Yaqian Huang ◽  
Zhao Yang ◽  
Yufei Chen ◽  
Jingang Zheng ◽  
...  
Keyword(s):  
Cartilage Oligomeric Matrix Protein ◽  
Matrix Protein ◽  
Therapeutic Strategies ◽  
At1 Receptor ◽  
Extracellular Matrix Protein ◽  
Binding Motif ◽  
Abdominal Aortic ◽  
Novel Therapeutic Strategies ◽  
G Protein Coupled

AbstractCompelling evidence has revealed that biased activation of G protein-coupled receptor (GPCR) signaling, including angiotensin II (AngII) receptor type 1 (AT1) signaling, plays pivotal roles in vascular homeostasis and injury, but whether a clinically relevant endogenous biased antagonism of AT1 signaling exists under physiological and pathophysiological conditions has not been clearly elucidated. Here, we show that an extracellular matrix protein, cartilage oligomeric matrix protein (COMP), acts as an endogenous allosteric biased modulator of the AT1 receptor and its deficiency is clinically associated with abdominal aortic aneurysm (AAA) development. COMP directly interacts with the extracellular N-terminus of the AT1 via its EGF domain and inhibits AT1-β-arrestin-2 signaling, but not Gq or Gi signaling, in a selective manner through allosteric regulation of AT1 intracellular conformational states. COMP deficiency results in activation of AT1a-β-arrestin-2 signaling and subsequent exclusive AAA formation in response to AngII infusion. AAAs in COMP–/– or ApoE–/– mice are rescued by AT1a or β-arrestin-2 deficiency, or the application of a peptidomimetic mimicking the AT1-binding motif of COMP. Explorations of the endogenous biased antagonism of AT1 receptor or other GPCRs may reveal novel therapeutic strategies for cardiovascular diseases.

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