25 Publication(s) found
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Cardiovascular System, Atherosclerosis
10. Nov 2010

Distribution, size, shape, growth potential and extent of abdominal aortic calcified deposits predict mortality in postmenopausal women

Aortic calcification is a major risk factor for death from cardiovascular disease. We investigated the relationship between mortality and the composite markers of number, size, morphology and distribution of calcified plaques in the lumbar aorta.

METHODS:
308 postmenopausal women aged 48-76 were…

Bone
4. Nov 2010

A quantitative assay for lysosomal acidification rates in human osteoclasts

The osteoclast initiates resorption by creating a resorption lacuna. The ruffled border surrounding the lacunae arises from exocytosis of lysosomes. To dissolve the inorganic phase of the bone, the vacuolar adenosine triphosphatase, located in the ruffled border, pumps protons into the resorption la…

Hepatic System, Non-Alcoholic Fatty Liver Disease
30. Oct 2010

Matrix metalloproteinase-9-mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis

BACKGROUND:
During fibrogenesis in the liver, in which excessive remodelling of the extracellular matrix (ECM) occurs, both the quantity of type III collagen (CO3) and levels of matrix metalloproteinases (MMPs), including MMP-9, increase significantly. MMPs play major roles in ECM remodelling, via …

Bone, Osteoporosis
26. Oct 2010

Screening of protein kinase inhibitors identifies PKC inhibitors as inhibitors of osteoclastic acid secretion and bone resorption

BACKGROUND:
Bone resorption is initiated by osteoclastic acidification of the resorption lacunae. This process is mediated by secretion of protons through the V-ATPase and chloride through the chloride antiporter ClC-7. To shed light on the intracellular signalling controlling extracellular acidifi…

Cardiovascular System, Atherosclerosis
8. Oct 2010

Macrophage-mediated proteolytic remodeling of the extracellular matrix in atherosclerosis results in neoepitopes: a potential new class of biochemical markers

Worldwide, cardiovascular disease (CVD) is the leading cause of death. Most CVD-related deaths are caused by years of preceding atherogenesis and the extensive development of atherosclerotic plaques, some of which may rupture to cause myocardial infarction. Macrophages are known to have a role in al…

Bone, Osteoporosis
5. Oct 2010

Enzyme-linked immunosorbent serum assays (ELISAs) for rat and human N-terminal pro-peptide of collagen type I (PINP)--assessment of corresponding epitopes

OBJECTIVES:
The present study describes two newly developed N-terminal pro-peptides of collagen type I (PINP) competitive enzyme-linked immunosorbent assays (ELISAs) for the assessment of corresponding PINP epitopes in the rat- and human species.

METHODS:
Monoclonal antibodies were raised again…

Bone
15. Aug 2010

Severe developmental bone phenotype in ClC-7 deficient mice

Bone development is dependent on the functionality of three essential cell types: chondrocytes, osteoclasts and osteoblasts. If any of these cell types is dysfunctional, a developmental bone phenotype can result. The bone disease osteopetrosis is caused by osteoclast dysfunction or impaired osteocla…

Hepatic System, Non-Alcoholic Fatty Liver Disease
10. Jul 2010

A novel assay for extracellular matrix remodeling associated with liver fibrosis: An enzyme-linked immunosorbent assay (ELISA) for a MMP-9 proteolytically revealed neo-epitope of type III collagen

OBJECTIVES:
Accumulation of extracellular matrix (ECM) components and increased matrix-metalloprotease (MMPs) activity are hallmarks of fibrosis. We developed an ELISA for quantification of MMP-9 derived collagen type III (CO3) degradation.

DESIGN AND METHODS:
A monoclonal antibody targeting a …

Extracellular Matrix Research, Biomarker position
10. Jul 2010

Novel combinations of Post-Translational Modification (PTM) neo-epitopes provide tissue-specific biochemical markers--are they the cause or the consequence of the disease?

The aim of this review is to discuss the potential usefulness of novel advances in the class of biochemical markers, neo-epitopes. Neo-epitopes are post-translational modifications (PTMs) of proteins formed by processes such as protease cleavage, citrullination, nitrosylation, glycosylation and isom…

Rheumatology, Osteoarthritis
17. Jun 2010

Biochemical markers identify influences on bone and cartilage degradation in osteoarthritis--the effect of sex, Kellgren-Lawrence (KL) score, body mass index (BMI), oral salmon calcitonin (sCT) treatment and diurnal variation

BACKGROUND:
Osteoarthritis (OA) involves changes in both bone and cartilage. These processes might be associated under some circumstances. This study investigated correlations between bone and cartilage degradation in patients with OA as a function of sex, Kellgren-Lawrence (KL) score, Body Mass In…

Bone
6. Jun 2010

Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes

The therapeutic goal of increasing bone mass by co-treatment of parathyroid hormone (PTH) and an osteoclast inhibitor has been complicated by the undefined contribution of osteoclasts to the anabolic activity of PTH. To determine whether active osteoclasts are required at the time of PTH administrat…

Bone, Osteoporosis
1. Jun 2010

Alterations in osteoclast function and phenotype induced by different inhibitors of bone resorption--implications for osteoclast quality

BACKGROUND:
Normal osteoclasts resorb bone by secretion of acid and proteases. Recent studies of patients with loss of function mutations affecting either of these processes have indicated a divergence in osteoclastic phenotypes. These difference in osteoclast phenotypes may directly or indirectly …

Rheumatology, Osteoarthritis
15. May 2010

Aggrecanase- and matrix metalloproteinase-mediated aggrecan degradation is associated with different molecular characteristics of aggrecan and separated in time ex vivo

Aggrecan is one of the first proteins to be depleted from articular cartilage in early osteoarthritis. We investigated the molecular differences between matrix metalloproteinase (MMP)- and aggrecanase-mediated aggrecan degradation, as a consequence of their distinct time-dependent degradation profil…

Bone
15. May 2010

Should biochemical markers of bone turnover be considered standard practice for safety pharmacology

The success in biomedical sciences such as genomics and proteomics is not paralleled in the medical product development methods. The consequence of this is a lack of translation into improved drug safety and efficacy. Therefore the US Food and Drug Administration (FDA) introduced the Critical Path I…

Cardiovascular System, Atherosclerosis
21. Apr 2010

Human macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processes

BACKGROUND:
Proteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture.The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular mat…

Rheumatology, Osteoarthritis
5. Apr 2010

Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes

BACKGROUND:
Calcitonin has been demonstrated to have chondroprotective effects under pre-clinical settings. It is debated whether this effect is mediated through subchondral-bone, directly on cartilage or both in combination. We investigated possible direct effects of salmon calcitonin on proteogly…

Hepatic System, Non-Alcoholic Fatty Liver Disease
1. Apr 2010

Procollagen type I N-terminal propeptide (PINP) is a marker for fibrogenesis in bile duct ligation-induced fibrosis in rats

BACKGROUND:
Fibrosis can be described as the excess deposition of extracellular matrix (ECM) components, such as collagens and proteoglycans. Fibrosis of the liver, which eventually leads to cirrhosis, is a major global health problem. Being able to measure fibrosis progression may enable timely pr…

Rheumatology, Osteoarthritis
28. Feb 2010

Which elements are involved in reversible and irreversible cartilage degradation in osteoarthritis?

Osteoarthritis (OA) is a disease of the entire joint. Different treatment strategies for OA have been proposed and tested clinically without the desired efficacy. One reason for the scarcity of current chondroprotective agents may be the insufficient understanding of the patho-physiology of the join…

Bone
18. Feb 2010

The effect of oral salmon calcitonin delivered with 5-CNAC on bone and cartilage degradation in osteoarthritic patients: a 14-day randomized study

BACKGROUND:
The aim of this study was to investigate the pharmacokinetic and pharmacodynamic parameters of oral salmon calcitonin (oSCT) administered over 14 days to men and women presenting with osteoarthritis (OA).

MATERIALS AND METHODS:
The study was a phase-I, 2-week, placebo-controlled, do…

Rheumatology, Osteoarthritis
15. Feb 2010

Application of biochemical markers in development of drugs for treatment of osteoarthritis

Osteoarthritis is a chronic disease for which no efficacious medical intervention is yet available. Recent disappointments in late-stage clinical development of disease-modifying osteoarthritic drugs (DMOADs) have precipitated efforts in biomarker discovery aimed at developing an analytical tool box…

Rheumatology
8. Feb 2010

Biochemical markers of joint tissue turnover

Recent disappointments in late stage developments of anti-osteoarthritic drugs have reinforced efforts to develop better biomarkers for application in both the drug development process as well as in the routine management of these patients. Here we provide a brief review of biochemical tests availab…

Rheumatology, Osteoarthritis
2. Feb 2010

Biglycan and fibromodulin have essential roles in regulating chondrogenesis and extracellular matrix turnover in temporomandibular joint osteoarthritis

The temporomandibular joint is critical for jaw movements and allows for mastication, digestion of food, and speech. Temporomandibular joint osteoarthritis is a degenerative disease that is marked by permanent cartilage destruction and loss of extracellular matrix (ECM). To understand how the ECM re…

Extracellular Matrix Research
28. Jan 2010

Serum markers of liver fibrosis: combining the BIPED classification and the neo-epitope approach in the development of new biomarkers

BACKGROUND:
Fibrosis is a central histological feature of chronic liver diseases and is characterized by the accumulation and reorganization of the extracellular matrix. The gold standard for assessment of fibrosis is histological evaluation of a percutaneous liver biopsy. Albeit a considerable eff…

Bone
16. Jan 2010

Investigations of inter- and intraindividual relationships between exposure to oral salmon calcitonin and a surrogate marker of pharmacodynamic efficacy

AIMS:
The aims of the study were to investigate interindividual variations in the bioavailability of salmon calcitonin (sCT) following single oral 0.8 mg doses at three different times of the day, and intraindividual variation in sCT bioavailability at each end of a 14-day treatment period. We also…