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Investigation of chondrocyte hypertrophy and cartilage calcification in a full-depth articular cartilage explants model.

February 1, 2013

Rheumatol Int

Abstract Articular cartilage deterioration, which includes cartilage degradation and chondrocyte hypertrophy, is a hallmark of degenerative joint diseases (DJD). Chondrocyte hypertrophy is initiated in the deep layer of the cartilage; thus, a robust explants model for investigation of hypertrophy should include this zone. The aim of this study was to characterize and investigate the hypertrophy-promoting […]

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The inhibitory effect of salmon calcitonin on tri-iodothyronine induction of early hypertrophy in articular cartilage.

January 1, 2012

PLoS One

Abstract OBJECTIVE Salmon calcitonin has chondroprotective effect both in vitro and in vivo, and is therefore being tested as a candidate drug for cartilage degenerative diseases. Recent studies have indicated that different chondrocyte phenotypes may express the calcitonin receptor (CTR) differentially. We tested for the presence of the CTR in chondrocytes from tri-iodothyronin (T3)-induced bovine […]

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Glucocorticoids exert context-dependent effects on cells of the joint in vitro.

December 11, 2011

Steroids

Abstract 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 osteoarthritis. This study aimed at characterizing the effect of glucocorticoids on chondrocytes, […]

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A quantitative assay for lysosomal acidification rates in human osteoclasts.

April 1, 2011

Assay Drug Dev Technol

Abstract 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 lacunae. The electroneutrality of the lacunae is maintained by chloride transport through […]

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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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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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MAPKs are essential upstream signaling pathways in proteolytic cartilage degradation–divergence in pathways leading to aggrecanase and MMP-mediated articular cartilage degradation.

March 1, 2010

Osteoarthritis Cartilage

Abstract OBJECTIVES Matrix metalloproteinases (MMPs) and aggrecanases are essential players in cartilage degradation. However, the signaling pathways that results in MMP and/or aggrecanase synthesis and activation are not well understood. We investigated the molecular events leading to MMP- and aggrecanase-mediated cartilage degradation. METHODS Cartilage degradation was induced in bovine articular cartilage explants by oncostatin M […]

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Cartilage formation measured by a novel PIINP assay suggests that IGF-I does not stimulate but maintains cartilage formation ex vivo.

June 1, 2009

Scand J Rheumatol

Abstract OBJECTIVES The aim of this study was to investigate the time-dependent effect of insulin-like growth factor-I (IGF)-I on cartilage, evaluated by a novel procollagen type II N-terminal propeptide (PIINP) formation assay. This was performed in a cartilage model. METHODS Bovine articular cartilage explants were cultured in Dulbecco’s modified Eagle’s medium (DMEM):F12 in the presence […]

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Cartilage degradation is fully reversible in the presence of aggrecanase but not matrix metalloproteinase activity.

January 1, 2008

Arthritis Res Ther

Abstract INTRODUCTION Physiological and pathophysiological cartilage turnover may coexist in articular cartilage. The distinct enzymatic processes leading to irreversible cartilage damage, compared with those needed for continuous self-repair and regeneration, remain to be identified. We investigated the capacity of repair of chondrocytes by analyzing their ability to initiate an anabolic response subsequent to three different […]

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