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Serum

CTX-I // C-Terminal Crosslinked Telopeptide of Type I Collagen

In bone, type I collagen constitute 90% of the organic matrix. Markers of bone resorption in serum or urine can be used to assess changes in bone resorption in various bone diseases or under treatment (Naylor and Eastell, 2012). Collagen in bone can be isomerized with racemization of the aspartic residues in the CTX telopeptide. The newly formed collagen is α isomerized and β isomerization occurs with aging (Garnero, 2012). In urine, the ratio between native and isomerized CTX can give an estimate of the extent of type I collagen isomerization in bone tissue (Cloos and Fledelius, 2000).

CS846 // Chondroitin Sulfate 846 Epitope

Chondroitin Sulfate epitope 846 (CS846) is an epitope present in newly synthetized agreccan molecules. CS846 is increased in joints and synovial fluid of patients with rheumatoid arthritis or osteoarthritis (Lohmander et al., 1999; Rizkalla et al., 1992; Verstappen et al., 2006). These increased levels in serum may reflect pathological increase in turnover of newly formed matrix, something that is not seen in healthy adult cartilage. To date, serum CS846 is also one of the 12 best-qualified biochemical markers that have shown associations with osteoarthritis (Hunter et al., 2014).

CREAT // Creatinine

Produced by muscle metabolism, creatinine is a degradation product of creatine phosphate and is essentially eliminated through the kidneys (Onuigbo and Agbasi, 2015). Creatinine metabolism is constant in one person and, in non-pathological situation, has a production rate equivalent to the renal extraction rate. Its concentration in serum is then dependent of the elimination capacity of the kidneys. Serum creatinine is the oldest and the most commonly used marker for estimating the glomerular filtration rate (Perrone et al., 1992).

COMP // Cartilage Oligomeric Matrix Protein

Cartilage oligomeric matrix protein (COMP) is also called thrombospondin-5 (TSP-5). COMP possess a RGD motif which allow interaction with integrins (Tan et al., 2009). COMP can bind to chondrocytes (the only cell type found in cartilage) and promote early stages of chondrogenic differentiation of mesenchymal stem cells, in association with bone morphogenic protein-2 (BMP-2)(Chen et al., 2005). Serum COMP is elevated in patients with diagnosed OA (level of evidence grade C) (Hoch et al., 2011).

COL4 // Type IV Collagen

Type Collagen IV is encoded by six genes: COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, and COL4A6 for the six collagen chain implicated in its composition: α1(IV) through α6(IV). The assembly of collagen IV network is highly regulated. Each of the six chains present the same features with three domains: short 7S N-Terminal, collagenous domain and non-collagenous domain (NC1) in C-terminal and can form three sets of helical molecules. Depending on the tissues the set of collagen type IV molecules is different.

CGA // Chromogranin A

Chromogranin A (CGA) is a neurosecretory protein initially identified in bovine adrenal medulla and produced simultaneously with catecholamines (Banks and Helle, 1965). CGA is the pro-hormone of at least three biologically active peptides generated by proteolytic cleavages: vasostatin, pancreastatin and parastatin, and also of two other peptides with antimicrobial and antifungal activities (catestatin and chromofungin).

Calcium

The adult body contains approximately 1kg of calcium. The majority of this calcium is found in the bone calcium hydroxyapatite. Calcium in the skeleton is critical for the strength and structure of bones but have also an important role in the maintenance of calcium homeostasis through bone formation and resorption. Calcium metabolism is regulated by parathyroid hormone (PTH), vitamin D, phosphate and magnesium (Goldstein, 1990; Ross, 2011).

Calcitonin

Calcitonin is produced in para-follicular C cells of the thyroid gland and is implicated in the regulation of circulating levels of calcium (Foster et al., 1964). Calcitonin is a peptide of 32 residues and circulates under different isoforms depending on the processing state of the hormone. This molecular heterogeneity might affect its measurement. Calcitonin levels may be increased in C cell diseases or in other diseases such as chronic renal failure, neuroendocrine tumors or autoimmune thyroid disease (Costante et al., 2009).

C2C // C-Terminal of the 3/4 Piece of Type II Collagen

In osteoarthritis, cartilage tissue is progressively degraded with denaturation of type II collagen by collagenases. MMP-1, MMP-8 and MMP-13, collagenases known to cleave type II collagen, are believed to act first on a unique site in the triple helix, producing approximately 3/4 ¾ and ¼ lengths denatured α chain (Billinghurst et al., 1997). The C-terminal specific neo-epitope of ¾ short type II collagen can be measured in serum of osteoarthritis patients.

C1, 2C // Type I and Type II Collagen 3/4C Short

In osteoarthritis, cartilage tissue is progressively degraded with denaturation of type II collagen by collagenases. MMP-1, MMP-8 and MMP-13, collagenases are known to cleave type II collagen, and are believed to act first on a unique site in the triple helix, producing approximately 3/4 and ¼ lengths denatured α chain (Billinghurst et al., 1997). These neo-epitopes can be measured in serum of osteoarthritis patients.

Bone TRAP // Bone Tartrate Resistant Acid Phosphatase

Tartrate-resistant acid phosphatase produced in bone-resorbing osteoclasts (TRACP 5b), or Bone Trap, is one of the two isoforms of TRACP (Janckila et al., 2003). The two isoforms differ in their content in sialic acid and TRACP 5a has a reduced activity at pH 6.0 (Halleen et al., 2000; Nenonen et al., 2005). Variation in serum levels of TRACP 5b isoform reflects modification in the bone resorption rate (Halleen et al., 2001).

BAP // Bone Alkaline Phosphatase

Alkaline phosphatase (ALP) catalyzes the hydrolysis of phosphomonoesters with alcohol and inorganic phosphate release. In human body, there are four ALP isoenzymes coded by four gene loci: tissue nonspecific ALP or liver/bone/kidney ALP, placental ALP, germ cell ALP and intestinal ALP. Liver, bone and kidney ALP are coded by the same gene but differs in posttranslational modification (Weiss et al., 1986). Bone ALP (BAP) is localized on the surface of osteoblasts and associated with bone formation. BAP can be released and measured in serum (Garnero and Delmas, 1993).

Anti-CCP // Antibody to Cyclic Citrullinated Peptide

The posttranslational protein modification which consists in conversion of peptidyl-arginine to peptidyl citrulline (citrullination) is an important process in the initiation of rheumatoid arthritis (Rantapää-Dahlqvist et al., 2003). Production of anti-CCP antibodies can lead to formation of immunogenic complex and, in the end, to rheumatoid arthritis (van Venrooij et al., 2011). Anti-CCP antibodies are one of the biomarkers used for the diagnosis of early rheumatoid arthritis.

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