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High throughput, quantitative analysis of human osteoclast differentiation and activity.

February 15, 2017

Anal Biochem

Abstract Osteoclasts are multinuclear cells that degrade bone under both physiological and pathophysiological conditions. Osteoclasts are therefore a major target of osteoporosis therapeutics aimed at preserving bone. Consequently, analytical methods for osteoclast activity are useful for the development of novel biomarkers and/or pharmacological agents for the treatment of osteoporosis. The nucleation state of an osteoclast […]

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The importance of extracellular matrix for cell function and in vivo likeness.

April 1, 2015

Exp Mol Pathol

Abstract OBJECTIVE Fibrotic diseases may be described as a disease of the extracellular matrix, where the balance between matrix formation and degradation has been shifted leading to an accumulation of matrix. Currently a fit for purpose model and readily available approach are adapted when doing cell cultures, which may not reflect physiology and pathophysiology optimally. […]

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Synovitis biomarkers: ex vivo characterization of three biomarkers for identification of inflammatory osteoarthritis.

January 1, 2015

Biomarkers

Abstract OBJECTIVE Characterize biomarkers measuring extracellular matrix turnover of inflamed osteoarthritis synovium. METHODS Human primary fibroblast-like synoviocytes and synovial membrane explants (SMEs) treated with various cytokines and growth factors were assessed by C1M, C3M, and acMMP3 in the conditioned medium. RESULTS TNFα significantly increased C1M up to seven-fold (p = 0.0002), C3M up to 24-fold (p = 0.0011), and […]

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Decline in calcitonin receptor expression in osteocytes with age.

May 1, 2014

J Endocrinol

Abstract We have previously shown that co-administration of the transient osteoclast inhibitor, salmon calcitonin (sCT), blunts the anabolic effect of parathyroid hormone (PTH) in young rats and increases osteocytic expression of the bone formation inhibitor sclerostin (Sost). To determine whether this also occurs in adult animals, we co-administered sCT with PTH to 6-month-old sham-operated (SHAM) […]

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A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts.

September 1, 2012

Bone

Abstract Osteoclasts are known to be important for the coupling process between bone resorption and formation. The aim of this study was to address when osteoclasts are anabolically active. Human monocytes were differentiated into mature osteoclasts by treatment with M-CSF and RANKL. Conditioned medium was collected from macrophages, pre-osteoclasts, and mature functional or non-resorbing osteopetrotic […]

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Tumor necrosis factor-α and receptor activator of nuclear factor-κB ligand augment human macrophage foam-cell destruction of extracellular matrix through protease-mediated processes.

February 1, 2012

Assay Drug Dev Technol

Abstract By secreting proteases such as cathepsins and matrix metalloproteinases (MMPs), macrophage foam cells may be a major cause of ruptured atherosclerotic plaques. The aims of the present study were to investigate in vitro role of human macrophage foam cells in degrading type I collagen, a major component of extracellular matrix (ECM) in plaques, and […]

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

October 26, 2010

BMC Musculoskelet Disord

Abstract 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 acidification, we screened a protein kinase inhibitor library in human osteoclasts. METHODS Human osteoclasts were […]

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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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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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