Cardiovascular System, Abdominal Aortic Aneurysm
11. Dec 2011
Abdominal aortic calcification quantified by the Morphological Atherosclerotic Calcification Distribution (MACD) index is associated with features of the metabolic syndrome
BACKGROUND:
Abdominal aortic calcifications (AAC) predict cardiovascular mortality. A new scoring model for AAC, the Morphological Atherosclerotic Calcification Distribution (MACD) index may contribute with additional information to the commonly used Aortic Calcification Severity (AC24) score, when…
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Authors:
- Barascuk N,
- Ganz M,
- Nielsen M,
- Register TC,
- Rasmussen LM,
- Karsdal MA,
- Christiansen C,
Bone, Osteoporosis
11. Dec 2011
Glucocorticoids exert context-dependent effects on cells of the joint in vitro
INTRODUCTION:
Glucocorticoids are known to attenuate bone formation in vivo leading to decreased bone volume and increased risk of fractures, whereas effects on the joint tissue are less characterized. However, glucocorticoids appear to have a reducing effect on inflammation and pain in osteoarthri…
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Journal:
Authors:
- Madsen SH,
- Andreassen KV,
- Christensen ST,
- Karsdal MA,
- Sverdrup FM,
- Bay-Jensen AC,
- Henriksen K,
Rheumatology, Osteoarthritis, Rheumatoid Arthritis
8. Dec 2011
Molecular serum and urine marker repertoire supporting clinical research on joint diseases
The need for improved analytical techniques in the study of slow, degenerative diseases such as rheumatoid arthritis and osteoarthritis has driven major efforts aimed at identifying biochemical markers of pathological processes in both diseases. A series of novel biochemical markers has surfaced and…
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Authors:
- Qvist P,
- Bay-Jensen AC,
- Christiansen C,
- Sondergaard BC,
- Karsdal MA,
Extracellular Matrix Research, Biomarker position
14. Nov 2011
Protein fingerprints - relying on and understanding the information of serological protein measurements
In 2004, the FDA has articulated a Critical Path Initiative to improve the efficiency of product development industry-wide, and brought attention to the pressing needs of defining new tools to better assess safety and effectiveness of new products. A better understanding of protein subtypes, protein…
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Authors:
- Karsdal MA,
- Delvin E,
- Christiansen C,
Bone
7. Nov 2011
Use of bone turnover markers in clinical osteoporosis assessment in women: current issues and future options
Monitoring bone turnover of the adult and aging skeleton is essential for optimal treatment of bone metabolic diseases, such as postmenopausal osteoporosis. Diagnosis of osteoporosis is based solely on dual-emission x-ray absorptiometry-based measurements of bone mineral density. However, within the…
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Hematology
22. Oct 2011
Assessment of proteolytic degradation of the basement membrane: a fragment of type IV collagen as a biochemical marker for liver fibrosis
BACKGROUND:
Collagen deposition and an altered matrix metalloproteinase (MMP) expression profile are hallmarks of fibrosis. Type IV collagen is the most abundant structural basement membrane component of tissue, which increases 14-fold during fibrogenesis in the liver. Proteolytic degradation of co…
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Authors:
- Veidal SS,
- Karsdal MA,
- Nawrocki A,
- Larsen MR,
- Dai Y,
- Zheng Q,
- Hägglund P,
- Vainer B,
- Skjøt-Arkil H,
- Leeming DJ,
Extracellular Matrix Research
16. Oct 2011
Serological biochemical markers of surrogate efficacy and safety as a novel approach to drug repositioning
How do pharmaceutical companies find new uses for old or failed drugs? Is there a way to 'manage serendipity' at the very first stage of identifying compounds that could be developed into new drugs? Several approaches are now being pursued by various companies that are dedicated to drug repositionin…
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Hepatic System, Alcoholic Liver Disease
16. Oct 2011
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…
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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,
Rheumatology, Osteoarthritis
13. Oct 2011
Identification of the calcitonin receptor in osteoarthritic chondrocytes
BACKGROUND:
Preclinical and clinical studies have shown that salmon calcitonin has cartilage protective effects in joint degenerative diseases, such as osteoarthritis (OA). However, the presence of the calcitonin receptor (CTR) in articular cartilage chondrocytes is yet to be identified. In this st…
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Journal:
Authors:
- Segovia-Silvestre T,
- Bonnefond C,
- Sondergaard BC,
- Christensen T,
- Karsdal MA,
- Bay-Jensen AC,
Endocrinology, Type 2-Diabetes
13. Oct 2011
A novel oral form of salmon calcitonin improves glucose homeostasis and reduces body weight in diet-induced obese rats
AIM:
To investigate the effects of acute and chronic administration of a novel oral formulation of salmon calcitonin (sCT) on glycaemic control, glucose homeostasis and body weight regulation in diet-induced obese (DIO) rats-an animal model of obesity-related insulin resistance and type 2 diabetes.…
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Authors:
- Feigh M,
- Henriksen K,
- Andreassen KV,
- Hansen C,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,
Hepatic System, Non-Alcoholic Fatty Liver Disease
16. Aug 2011
Immunological detection of the type V collagen propeptide fragment, PVCP-1230, in connective tissue remodeling associated with liver fibrosis
AIM:
Liver fibrosis involves excessive remodeling and deposition of fibrillar extracellular matrix (ECM) components, which leads to malfunction of the organ, causing significant morbidity and mortality. The aim of this study was to assess whether levels of a type V collagen fragment, the propeptide…
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Authors:
- Vassiliadis E,
- Veidal SS,
- Simonsen H,
- Larsen DV,
- Vainer B,
- Chen X,
- Zheng Q,
- Karsdal MA,
- Leeming DJ,
Hepatic System, Non-Alcoholic Steatohepatitis
9. Aug 2011
Circulating CO3-610, a degradation product of collagen III, closely reflects liver collagen and portal pressure in rats with fibrosis
BACKGROUND:
Hepatic fibrosis is characterized by intense tissue remodeling, mainly driven by matrix metalloproteinases. We previously identified CO3-610, a type III collagen neoepitope generated by matrix metalloproteinase (MMP)-9, and tested its performance as a fibrosis marker in rats with bile-d…
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Authors:
- Segovia-Silvestre T,
- Reichenbach V,
- Fernández-Varo G,
- Vassiliadis E,
- Barascuk N,
- Morales-Ruiz M,
- Karsdal MA,
- Jiménez W,
Oncology, Breast
3. Aug 2011
A novel and automatic mammographic texture resemblance marker is an independent risk factor for breast cancer
OBJECTIVE:
We investigated whether breast cancer is predicted by a breast cancer risk mammographic texture resemblance (MTR) marker.
METHODS:
A previously published case-control study included 495 women of which 245 were diagnosed with breast cancer. In baseline mammograms, 2-4 years prior to d…
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Authors:
- Nielsen M,
- Karemore G,
- Loog M,
- Raundahl J,
- Karssemeijer N,
- Otten JD,
- Karsdal MA,
- Vachon CM,
- Christiansen C,
Bone
22. Jul 2011
Vertebral fracture risk (VFR) score for fracture prediction in postmenopausal women
SUMMARY:
Early prognosis of osteoporosis risk is not only important to individual patients but is also a key factor when screening for osteoporosis drug trial populations. We present an osteoporosis fracture risk score based on vertebral heights. The score separated individuals who sustained fractu…
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Authors:
- Lillholm M,
- Ghosh A,
- Pettersen PC,
- de Bruijne M,
- Dam EB,
- Karsdal MA,
- Christiansen C,
- Genant HK,
- Nielsen M,
Rheumatology, Osteoarthritis
14. Jul 2011
Characterization of an Ex vivo Femoral Head Model Assessed by Markers of Bone and Cartilage Turnover
OBJECTIVE:
The pathophysiology of osteoarthritis involves the whole joint and is characterized by cartilage degradation and altered subchondral bone turnover. At present, there is a need for biological models that allow investigation of the interactions between the key cellular players in bone/cart…
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Authors:
- Madsen SH,
- Goettrup AS,
- Thomsen G,
- Christensen ST,
- Schultz N,
- Henriksen K,
- Bay-Jensen AC,
- Karsdal MA,
Cardiovascular System, Atherosclerosis
11. Jul 2011
Development and validation of an enzyme-linked immunosorbent assay for the quantification of a specific MMP-9 mediated degradation fragment of type III collagen--A novel biomarker of atherosclerotic plaque remodeling
Degradation of collagen in the arterial wall by matrix metalloproteinases is the hallmark of atherosclerosis. We have developed an ELISA for the quantification of type III collagen degradation mediated by MMP-9 in urine.
DESIGN AND METHODS:
A monoclonal antibody targeting a specific MMP-9 genera…
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Authors:
- Barascuk N,
- Vassiliadis E,
- Larsen L,
- Wang J,
- Zheng Q,
- Xing R,
- Cao Y,
- Crespo C,
- Lapret I,
- Sabatini M,
- Villeneuve N,
- Vilaine JP,
- Rasmussen LM,
- Register TC,
- Karsdal MA,
Bone
15. Jun 2011
Degradation of the organic phase of bone by osteoclasts: a secondary role for lysosomal acidification
Osteoclasts degrade bone matrix by secretion of hydrochloric acid and proteases. We studied the processes involved in the degradation of the organic matrix of bone in detail and found that lysosomal acidification is involved in this process and that MMPs are capable of degrading the organic matrix i…
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Authors:
- Henriksen K,
- Sørensen MG,
- Nielsen RH,
- Gram J,
- Schaller S,
- Dziegiel MH,
- Everts V,
- Bollerslev J,
- Karsdal MA,
Cardiovascular System, Atherosclerosis
11. Jun 2011
Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice
AIM:
Arterial extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs) is one of the major hallmarks of atherosclerosis. Mimecan, also known as osteoglycin has been implicated in the integrity of the ECM. This study assessed the validity of an enzyme-linked immunosorbent assay (ELI…
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Journal:
Authors:
- Barascuk N,
- Vassiliadis E,
- Zheng Q,
- Wang Y,
- Wang W,
- Larsen L,
- Rasmussen LM,
- Karsdal MA,
Bone
11. Jun 2011
Dissociation of bone resorption and bone formation in adult mice with a non-functional V-ATPase in osteoclasts leads to increased bone strength
Osteopetrosis caused by defective acid secretion by the osteoclast, is characterized by defective bone resorption, increased osteoclast numbers, while bone formation is normal or increased. In contrast the bones are of poor quality, despite this uncoupling of formation from resorption.To shed light …
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Authors:
- Henriksen K,
- Flores C,
- Thomsen JS,
- Brüel AM,
- Thudium CS,
- Neutzsky-Wulff AV,
- Langenbach GE,
- Sims N,
- Askmyr M,
- Martin TJ,
- Everts V,
- Karsdal MA,
- Richter J,
Hepatic System, Non-Alcoholic Fatty Liver Disease
9. Jun 2011
MMP mediated degradation of type VI collagen is highly associated with liver fibrosis--identification and validation of a novel biochemical marker assay
BACKGROUND AND AIMS:
During fibrogenesis, in which excessive remodeling of the extracellular matrix occurs, both the quantity of type VI collagen and levels of matrix metalloproteinases, including MMP-2 and MMP-9, increase significantly. Proteolytic degradation of type VI collagen into small fragme…
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Journal:
Authors:
- Veidal SS,
- Karsdal MA,
- Vassiliadis E,
- Nawrocki A,
- Larsen MR,
- Nguyen QH,
- Hägglund P,
- Luo Y,
- Zheng Q,
- Vainer B,
- Leeming DJ,
Endocrinology, Type 2-Diabetes
27. May 2011
Efficacy and safety of the PPARγ partial agonist balaglitazone compared with pioglitazone and placebo: a phase III, randomized, parallel-group study in patients with type 2 diabetes on stable insulin therapy
BACKGROUND:
Treatment of patients with perioxisome proliferator-activated receptor-γ full agonists are associated with weight gain, heart failure, peripheral oedema, and bone loss. However, the safety of partial perioxisome proliferator-activated receptor-γ agonists has not been established in a cl…
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Journal:
Authors:
- Henriksen K,
- Byrjalsen I,
- Qvist P,
- Beck-Nielsen H,
- Hansen G,
- Riis BJ,
- Perrild H,
- Svendsen OL,
- Gram J,
- Karsdal MA,
- Christiansen C,
- BALLET Trial Investigators,
Extracellular Matrix Research
16. May 2011
Post-translational modifications of the extracellular matrix are key events in cancer progression: opportunities for biochemical marker development
The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, designated neoepitopes. Neoepitopes are post-translational modifications (PTMs) of proteins and are derived by processes, such as protease cleavage, citrullination, nitrosylation, glycosylation and…
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Authors:
- Leeming DJ,
- Bay-Jensen AC,
- Vassiliadis E,
- Larsen MR,
- Henriksen K,
- Karsdal MA,
Rheumatology, Osteoarthritis
19. Apr 2011
Oral salmon calcitonin reduces cartilage and bone pathology in an osteoarthritis rat model with increased subchondral bone turnover
OBJECTIVES:
Traumatic osteoarthritis (OA) is possibly augmented by effects from loss of sex hormones. Salmon calcitonin is shown to reduce OA pathogenesis and bone resorption. We investigated the effects of oral salmon calcitonin treatment and ovariectomy on cartilage and bone pathology in a trauma…
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Journal:
Authors:
- Nielsen RH,
- Bay-Jensen AC,
- Byrjalsen I,
- Karsdal MA,
Bone, Osteoporosis
14. Apr 2011
Strontium ranelate effect in postmenopausal women with different clinical levels of osteoarthritis
OBJECTIVE:
The objective of this post hoc analysis was to investigate the effect of strontium ranelate on a cartilage degradation marker in postmenopausal women who participated in a randomized, placebo-controlled osteoporosis study. Women were stratified according to reported symptoms of osteoarth…
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Authors:
- Alexandersen P,
- Karsdal MA,
- Byrjalsen I,
- Christiansen C,
Rheumatology, Osteoarthritis
13. Apr 2011
Enzyme-linked immunosorbent assay (ELISAs) for metalloproteinase derived type II collagen neoepitope, CIIM--increased serum CIIM in subjects with severe radiographic osteoarthritis
OBJECTIVES:
In joint degenerative diseases, the collagens are degraded by matrix metalloproteinases and protein fragments are released to serum as potential biomarkers.
METHODS:
A collagen type II specific neoepitope, CIIM, was identified (…RDGAAG(1053)) by mass spectrometry. Two ELISAs against…
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Journal:
Authors:
- Bay-Jensen AC,
- Liu Q,
- Byrjalsen I,
- Li Y,
- Wang J,
- Pedersen C,
- Leeming DJ,
- Dam EB,
- Zheng Q,
- Qvist P,
- Karsdal MA,
Rheumatology, Spondyloarthropathies
8. Apr 2011
Biochemical markers of ongoing joint damage in rheumatoid arthritis--current and future applications, limitations and opportunities
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease associated with potentially debilitating joint inflammation, as well as altered skeletal bone metabolism and co-morbid conditions. Early diagnosis and aggressive treatment to control disease activity offers the highest likelihood of …
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Journal:
Authors:
- Karsdal MA,
- Woodworth T,
- Henriksen K,
- Maksymowych WP,
- Genant H,
- Vergnaud P,
- Christiansen C,
- Schubert T,
- Qvist P,
- Schett G,
- Platt A,
- Bay-Jensen AC,
Bone
5. Apr 2011
Lessons learned from the development of oral calcitonin: the first tablet formulation of a protein in phase III clinical trials
Oral delivery of proteins has been hampered by an array of difficulties. However, promising novel oral delivery systems have been developed. 5-CNAC, formulated with the peptide salmon calcitonin, is in phase III clinical trials for the treatment of osteoporosis or osteoarthritis and could become the…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Bay-Jensen AC,
- Molloy B,
- Arnold M,
- John MR,
- Byrjalsen I,
- Azria M,
- Riis BJ,
- Qvist P,
- Christiansen C,
Rheumatology, Systemic Sclerosis
29. Mar 2011
Measurement of matrix metalloproteinase 9-mediated collagen type III degradation fragment as a marker of skin fibrosis
BACKGROUND:
The current study utilized a Bleomycin-induced model of skin fibrosis to investigate the neo-epitope CO3-610 (KNGETGPQGP), a fragment of collagen III released during matrix metalloproteinase-9 (MMP9) degradation of the protein, we have previously described as a novel biomarker for liver…
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Journal:
Authors:
- Vassiliadis E,
- Veidal SS,
- Barascuk N,
- Mullick JB,
- Clausen RE,
- Larsen L,
- Simonsen H,
- Larsen DV,
- bay,
- Segovia-Silvestre T,
- Leeming DJ,
- Karsdal MA,
Hepatic System, Alcoholic Liver Disease
24. Mar 2011
Measurement of CO3-610, a potential liver biomarker derived from matrix metalloproteinase-9 degradation of collagen type III, in a rat model of reversible carbon-tetrachloride-induced fibrosis
BACKGROUND AND AIM:
The current study utilized a carbon tetrachloride (CCl(4))-induced liver fibrosis model to measure levels of the MMP9-mediated collagen type III degradation fragment CO3-610 (site of cleavage: KNGETGPQGP), during disease progression and regression, and to investigate a potential…
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Journal:
Authors:
- Vassiliadis E,
- Larsen DV,
- Clausen RE,
- Veidal SS,
- Barascuk N,
- Larsen L,
- Simonsen H,
- Silvestre TS,
- Hansen C,
- Overgaard T,
- Leeming DJ,
- Karsdal MA,
Rheumatology, Osteoarthritis
15. Mar 2011
A microarray analysis of full depth knee cartilage of ovariectomized rats
BACKGROUND:
This short communication focuses the on articular cartilage and the subchondral bone, both of which play important roles in the development of osteoarthritis (OA). There are indications that estrogen-deficiency, as the post-menopausal state, accelerate the development of OA.
FINDINGS…
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Journal:
Authors:
- Bay-Jensen AC,
- Nielsen RH,
- Segovia-Silvestre T,
- Azria M,
- Staedtler F,
- Letzkus M,
- Hartmann N,
- Brachat AH,
- Karsdal MA,
Oncology, Bone
3. Mar 2011
Serum N-Terminal Propeptide of Collagen Type I is Associated with the Number of Bone Metastases in Breast and Prostate Cancer and Correlates to Other Bone Related Markers
BACKGROUND:
A number of biomarkers have been proven potentially useful for their ability to indicate bone metastases (BM) in cancer patients. The aim of this study was to investigate the relative utility of a newly developed N-terminal propeptide of collagen type I (PINP) human serum assay for the …
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Journal:
Authors:
- Leeming DJ,
- Koizumi M,
- Qvist P,
- Barkholt V,
- Zhang C,
- Henriksen K,
- Byrjalsen I,
- Karsdal MA,
Bone
15. Feb 2011
Osteoclast activity and subtypes as a function of physiology and pathology--implications for future treatments of osteoporosis
Osteoclasts have traditionally been associated exclusively with catabolic functions that are a prerequisite for bone resorption. However, emerging data suggest that osteoclasts also carry out functions that are important for optimal bone formation and bone quality. Moreover, recent findings indicate…
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Journal:
Authors:
- Henriksen K,
- Bollerslev J,
- Everts V,
- Karsdal MA,
Bone
10. Jan 2011
Imatinib mesylate does not increase bone volume in vivo
Imatinib mesylate is a tyrosine kinase inhibitor used in the management of disorders in which activation of c-Abl, PDGFR, or c-Kit signaling plays a critical role. In vitro, imatinib stimulates osteoblast differentiation, inhibits osteoblast proliferation and survival, and decreases osteoclast devel…
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Authors:
- O'Sullivan S,
- Naot D,
- Callon KE,
- Watson M,
- Gamble GD,
- Ladefoged M,
- Karsdal MA,
- Browett P,
- Cornish J,
- Grey A,
Rheumatology, Osteoarthritis
3. Jan 2011
Tummala SDiagnosis of Osteoarthritis by Cartilage Surface Smoothness Quantified Automatically from Knee MRI
OBJECTIVE:
We investigated whether surface smoothness of articular cartilage in the medial tibiofemoral compartment quantified from magnetic resonance imaging (MRI) could be appropriate as a diagnostic marker of osteoarthritis (OA).
METHOD:
At baseline, 159 community-based subjects aged 21 to 8…
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Journal:
Authors:
- Tummala S,
- Bay-Jensen AC,
- Karsdal MA,
- Dam EB,