Serological Assessment of the Quality of Wound Healing Processes in Crohn's Disease.
BACKGROUND AND AIMS:
Crohn's disease (CD) is a chronic inflammatory condition characterized by continuous mucosal damage and ongoing wound healing of the intestines. The fibrinolytic system is involved in early parts of the wound healing process. Fibrin is a key mediator of primary blood clot forma…
Journal:
Authors:
- Sun S,
- Karsdal MA,
- Mortensen JH,
- Luo Y,
- Kjeldsen J,
- Krag A,
- Jensen MD,
- Bay-Jensen AC,
- Manon-Jensen T,
Circulating Biomarkers of Testosterone's Anabolic Effects on Fat-Free Mass
BACKGROUND:
Biomarkers that predict response to anabolic therapies could expedite the development of function promoting anabolic drugs. This study aimed to identify serum biomarkers that are responsive to testosterone administration and associated with increases in fat-free mass (FFM).
METHODS:
…
Journal:
Authors:
- Huang G,
- Rocha GV,
- Pencina KM,
- Cox K,
- Krishnan V,
- Henriksen K,
- Mitchell P,
- Sissons SE,
- Li Z,
- Nedergaard AF,
- Karsdal MA,
- Sun S,
- Storer TW,
- Basaria S,
- Bhasin S,
Initiation of the Wound Healing Cascade in Inflammatory Bowel Disease: Assessment of Von Willebrand Factor ADAMTS-13 Processing and Formation in Crohn’s Disease
Background: Crohn’s disease (CD) is a chronic inflammatory condition of the intestinal tract resulting in severe intestinal tissue
damage. The concept of mucosal healing has therefore gained significant interest as a therapeutic end point in the treatment of
inflammatory bowel disease (IBD). Given…
Authors:
- Manon-Jensen T,
- Langholm LL,
- Sun S,
- Mortensen JH,
- He Y,
- Krag A,
- Jensen MD,
- Bay-Jensen AC,
- Kjeldsen J,
- Karsdal MA,
Alterations in non-type I collagen biomarkers in osteogenesis imperfecta.
Osteogenesis imperfecta (OI) is a rare disorder of connective tissue caused by abnormalities in the synthesis or processing of type I collagen. Type I collagen is the most abundant type of collagen and is expressed in almost all connective tissues. Given that type I collagen interacts with other col…
Journal:
Authors:
- Nicol L,
- Morar P,
- Wang Y,
- Henriksen K,
- Sun S,
- Karsdal MA,
- Smith R,
- Nagamani SCS,
- Shapiro J,
- Lee B,
- Orwoll E,
Lung tissue destruction by proteinase 3 and cathepsin G mediated elastin degradation is elevated in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is characterized by high levels of protease activity leading to degradation of elastin followed by loss of elasticity of the lung and the development of emphysema. Elastin is an essential structural component of the lung parenchyma to support the expansio…
Journal:
Authors:
- Gudmann NS,
- Manon-Jensen T,
- Sand JMB,
- Diefenbach C,
- Sun S,
- Danielsen A,
- Karsdal MA,
- Leeming DJ,
Lung tissue destruction by proteinase 3 and cathepsin G mediated elastin degradation is elevated in chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is characterized by high levels of protease activity leading to degradation of elastin followed by loss of elasticity of the lung and the development of emphysema. Elastin is an essential structural component of the lung parenchyma to support the expansio…
Journal:
Authors:
- Gudmann NS,
- Manon-Jensen T,
- Sand JM,
- Diefenbach C,
- Sun S,
- Danielsen A,
- Karsdal MA,
- Leeming DJ,
A fragment of SPARC reflecting increased collagen affinity shows pathological relevance in lung cancer - implications of a new collagen chaperone function of SPARC
The matricellular protein SPARC (secreted proteome acidic and rich in cysteine) is known to bind collagens and regulate fibrillogenesis. Cleavage of SPARC at a single peptide bond, increases the affinity for collagens up to 20-fold. To investigate if this specific cleavage has pathological relevance…
Journal:
Authors:
- Kehlet SN,
- Manon-Jensen T,
- Sun S,
- Brix S,
- Karsdal MA,
- Leeming DJ,
- Willumsen N,
Tumstatin, a Matrikine Derived from Collagen Type IVα3, is Elevated in Serum from Patients with Non-Small Cell Lung Cancer
OBJECTIVES
Fibrosis and cancer are characterized by extracellular matrix (ECM) remodeling. The basement membrane is mainly composed by collagen type IV and laminin. Tumstatin is a matrix metalloproteinase-9 (MMP-9) generated matrikine of collagen type IV α3 chain. We evaluated the potential of tums…
Journal:
Authors:
- Nielsen SH,
- Willumsen N,
- Brix S,
- Sun S,
- Manon-Jensen T,
- Karsdal MA,
- Genovese F,
The endothelial specific isoform of type XVIII collagen correlates to annual bleeding rate in haemophilia patients
INTRODUCTION:
The medical need in the haemophilic (HF) field to reduce bleeding incidents requires measurement of the annual bleeding rate (ABR) in haemophiliacs. Vascular rupture is associated with damage to the vascular endothelium causing exposure of the basement membrane. Endothelial cells and …
Journal:
Authors:
- Kjeld NG,
- Hua B,
- Karsdal MA,
- Sun S,
- Manon-Jensen T,
Increased basement membrane turnover and strongly attenuated interstitial matrix turnover is a key pathological feature of haemophilia
Altered extracellular matrix (ECM) turnover is a central pathological feature of many diseases. The ECM is a meshwork of molecules that provides structural support to cells throughout the body. It consists mainly of two membranes: the interstitial matrix, which is present between parenchymal cells i…
Journal:
Authors:
- Manon-Jensen T,
- Hua BL,
- Olsen EHN,
- Sun S,
- Gudme CN,
- Li J,
- Lei W,
- Vandahl B,
- Roepstorff K,
- Kjelgaard-Hansen M,
- Zhao Y,
- Karsdal MA,
Suppression of active, but not total MMP-3, is associated with treatment response in a phase III clinical study of rheumatoid arthritis
OBJECTIVE:
Biologics for rheumatoid arthritis (RA) patients with moderate to severe disease may preserve joint function. Matrix metalloproteinase 3 (MMP-3), a key tissue degrading protease, is highly elevated in RA. MMP-3, which measures the total pool of circulating MMP-3 species (cMMP3), is a com…
Journal:
Authors:
- Siebuhr AS,
- Kjelgaard-Petersen CF,
- Sun S,
- Byrjalsen I,
- Christiansen C,
- Karsdal MA,
- Bay-Jensen AC,
Serological biomarkers detect active joint destruction and inflammation in patients with haemophilic arthropathy
INTRODUCTION:
Progressive arthropathy caused by recurrent joint bleeds is a severe complication in haemophilia.
AIM:
We investigated whether biomarkers of cartilage and bone degradation, and inflammation were altered in haemophilia patients and whether these biomarkers could identify haemophili…
Journal:
Authors:
- Hua B,
- Olsen EHN,
- Sun S,
- Gudme CN,
- Wang L,
- Vandahl B,
- Roepstorff K,
- Kjelgaard-Hansen M,
- Sørensen BB,
- Zhao Y,
- Karsdal MA,
- Manon-Jensen T,
Collagen Type III and VI Turnover in Response to Long-Term Immobilization
BACKGROUND:
Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarker…
Journal:
Authors:
- Sun S,
- Henriksen K,
- Karsdal MA,
- Byrjalsen I,
- Rittweger J,
- Armbrecht G,
- Belavý DL,
- Felsenberg D,
- Nedergaard AF,
Accelerated extracellular matrix turnover during exacerbations of COPD
BACKGROUND:
Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression. However, the effect on tissue structure and turnover is not well described. There is an urgent clinical need for biomarkers of disease activity associated with disease progress…
Journal:
Authors:
- Sand JM,
- Knox AJ,
- Lange P,
- Sun S,
- Kristensen JH,
- Leeming DJ,
- Karsdal MA,
- Bolton CE,
- Johnson SR,
Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy
PURPOSE:
In this study we sought to determine whether a Titin peptide fragment can serve as a clinical biomarker for changes in muscle mass.
METHODS:
Mass spectrometry was used to identify Titin fragment in urine. An antibody against this Titin sequence was raised and used to develop a competit…
Journal:
Authors:
- Sun S,
- Henriksen K,
- Karsdal MA,
- Armbrecht G,
- Belavý DL,
- Felsenberg D,
- Rittweger J,
- Wang Y,
- Zheng Q,
- Nedergaard AF,
The active form of MMP-3 is a marker of synovial inflammation and cartilage turnover in inflammatory joint diseases
BACKGROUND:
Matrix metalloproteinase-3 (MMP-3) plays an important role in the pathology of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Measurement of active MMP-3 in clinical samples could provide information about progression of rheumatoid diseases, and potentially response to treat…
Journal:
Authors:
- Sun S,
- Bay-Jensen AC,
- Karsdal MA,
- Siebuhr AS,
- Zheng Q,
- Maksymowych WP,
- Christiansen TG,
- Henriksen K,
Type VI collagen turnover-related peptides-novel serological biomarkers of muscle mass and anabolic response to loading in young men
BACKROUND:
Immobilization-induced loss of muscle mass is a complex phenomenon with several parallels to sarcopenic and cachectic muscle loss. Muscle is a large organ with a protein turnover that is orders of magnitude larger than most other tissues. Thus, we hypothesize that muscle loss and regain …
Journal:
Authors:
- Nedergaard A,
- Sun S,
- Karsdal MA,
- Henriksen K,
- Kjær M,
- Lou Y,
- He Y,
- Zheng Q,,
- Suetta C,
The development and characterization of an ELISA specifically detecting the active form of cathepsin K
OBJECTIVE:
Cathepsin K plays essential roles in bone resorption and is intensely investigated as a therapeutic target for the treatment of osteoporosis. Hence an assessment of the active form of cathepsin K may provide important biological information in metabolic bone diseases, such as osteoporosi…
Journal:
Authors:
- Sun S,
- Karsdal MA,
- Bay-Jensen AC,
- Sørensen MG,
- Zheng Q,
- Dziegiel MH,
- Maksymowych WP,
- Henriksen K,
A MMP derived versican neo-epitope is elevated in plasma from patients with atherosclerotic heart disease
Extracellular matrix remodelling is a prerequisite for plaque rupture in atherosclerotic lesion. Versican, an extracellular matrix proteoglycan present in normal and atherosclerotic arteries is a substrate for matrix metalloproteinases (MMPs) present in macrophage rich areas. The aim of the current …
Journal:
Authors:
- Barascuk N,
- Genovese F,
- Larsen L,
- Byrjalsen I,
- Zheng Q,
- Sun S,
- Hosbond S,
- Poulsen TS,
- Diederichsen A,
- Jensen JM,
- Mickley H,
- Register TC,
- Rasmussen LM,
- Leeming DJ,
- Christiansen C,
- Karsdal MA,
The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters
AIM:
The present study describes the assessment of true formation of type III collagen in different pathologies using a neo-epitope specific competitive Enzyme-linked immunosorbent assay (ELISA) towards the N-terminal propeptide of type III collagen (PRO-C3).
METHODS:
The monoclonal antibody wa…
Journal:
Authors:
- Nielsen MJ,
- Nedergaard AF,
- Sun S,
- Veidal SS,
- Larsen L,
- Zheng Q,
- Suetta C,
- Henriksen K,
- Christiansen C,
- Karsdal MA,
- Leeming DJ,
Serological muscle loss biomarkers: an overview of current concepts and future possibilities
BACKGROUND:
The skeletal muscle mass is the largest organ in the healthy body, comprising 30-40 % of the body weight of an adult man. It confers protection from trauma, locomotion, ventilation, and it represents a "sink" in glucose metabolism and a reservoir of amino acids to other tissues such as …
Journal:
Authors:
- Nedergaard A,
- Karsdal MA,
- Sun S,
- Henriksen K,
MMP mediated type V collagen degradation (C5M) is elevated in ankylosing spondylitis
OBJECTIVES:
Type V collagen has been demonstrated to control fibril formation. The aim of this study was to develop an ELISA capable of detecting a fragment of type V collagen generated by MMP-2/9 and to evaluate the assay as biomarker for ankylosing spondylitis (AS).
DESIGN AND METHODS:
A frag…
Journal:
Authors:
- Veidal SS,
- Larsen DV,
- Chen X,
- Sun S,
- Zheng Q,
- Bay-Jensen AC,
- Leeming DJ,
- Nawrocki A,
- Larsen MR,
- Schett G,
- Karsdal MA,
A novel marker for assessment of liver matrix remodeling: an enzyme-linked immunosorbent assay (ELISA) detecting a MMP generated type I collagen neo-epitope (C1M)
A competitive enzyme-linked immunosorbent assay (ELISA) for detection of a type I collagen fragment generated by matrix metalloproteinases (MMP) -2, -9 and -13, was developed (CO1-764 or C1M). The biomarker was evaluated in two preclinical rat models of liver fibrosis: bile duct ligation (BDL) and c…
Journal:
Authors:
- Leeming DJ,
- He Y,
- Veidal SS,
- Nguyen Q,
- Larsen D,
- Koizumi M,
- Segovia-Silvestre T,
- Zhang C,
- Zheng Q,
- Sun S,
- Cao Y,
- Barkholt V,
- Hägglund P,
- Bay-Jensen A,
- Qvist P,
- Karsdal MA,