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Severe developmental bone phenotype in ClC-7 deficient mice.

August 15, 2010

Dev Biol

Abstract 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 osteoclastogenesis, leading to increased bone mass. In ClC-7 deficient mice, which display severe […]

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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.

July 1, 2010

Clin Biochem

Abstract 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 specific MMP-9 cleaved fragment of CO3 was used for development of a competitive ELISA. The assay […]

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

July 1, 2010

Clin Biochem

Abstract 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 isomerization. Each modification results from a specific local physiological or pathobiologial process. Identification of each […]

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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.

June 17, 2010

BMC Musculoskelet Disord

Abstract 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 Index (BMI), oral salmon calcitonin (sCT) treatment and diurnal variation. METHODS This study […]

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

June 1, 2010

BMC Musculoskelet Disord

Abstract 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 have secondary effects on bone remodeling, a process which is of importance for […]

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

May 1, 2010

Biomarkers

Abstract 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 profiles. Cartilage degradation was induced by cytokine stimulation in bovine articular cartilage explants and quantified by a […]

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

May 1, 2010

Biomarkers

Abstract 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 Initiative in 2004 to modernize drug development and […]

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

April 21, 2010

BMC Cardiovasc Disord

Abstract 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 matrix (ECM) of atherosclerotic plaques by cathepsin K mediated processes. METHODS We […]

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

April 5, 2010

BMC Musculoskelet Disord

Abstract 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 proteoglycans and collagen-type-II synthesis in osteoarthritic (OA) cartilage. METHODS Human OA cartilage explants were cultured with […]

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

April 1, 2010

Fibrogenesis Tissue Repair

Abstract 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 preventative intervention. The aim of the current study was to investigate […]

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