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

February 1, 2010

Rheumatol Int

Abstract 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 joint and whether the joint damage is reversible or irreversible. In […]

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Biochemical markers of joint tissue turnover.

February 1, 2010

Assay Drug Dev Technol

Abstract 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 available for the study of tissue turnover in each of the […]

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

February 1, 2010

Biomarkers

Abstract 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 with the potential to improve the clinical development process. In this review, we seek to provide […]

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

January 1, 2010

Dis Markers

Abstract 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 effort have been invested in finding alternative non-invasive approaches, these have not been […]

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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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Biochemical markers and the FDA Critical Path: how biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development.

May 1, 2009

Biomarkers

Abstract The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, neoepitopes, in the context of the US Food and Drug Administration (FDA) Critical Path Initiative, which emphasizes biomarkers of safety and efficacy as areas of pivotal interest. Examples of protein degradation fragments–neoepitopes–that have proven useful for […]

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The disease modifying osteoarthritis drug (DMOAD): Is it in the horizon?

July 1, 2008

Pharmacol Res

Abstract Till date, the pharmaceutical industry has failed to bring effective and safe disease modifying osteoarthritic drugs (DMOADs) to the millions of patients suffering from this serious and deliberating disease. We provide a review of recent data reported on the investigation of DMOADs in clinical trials, including compounds inhibiting matrix-metalloproteinases (MMPs), bisphosphonates, cytokine blockers, calcitonin, […]

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