Background: Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by non-functional osteoclasts and a fatal outcome early in childhood. About 50% of patients have mutations in the TCIRG1 gene.Methods: IMO iPSCs were generated from a patient carrying a homozygous c....

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Osteoarthritis (OA) is a disease of the whole joint, including synovium, bone and cartilage. OA is a slow degenerative and very heterogeneous disease, with both varying levels of disease activity and progression. Biomarkers are urgently needed to assist drug developers in selecting and developing th...

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September 30, 2019

Journal:
Clin Exp Rheumatol

Author:
Karsdal MA, Henriksen K, Bay-Jensen AC

Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by nonfunctional osteoclasts. Approximately 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. Gene therapy represents a potential alternative treatment

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OBJECTIVE: The objective was to investigate blood-based biomarkers of type I (PRO-C1), III (PRO-C3) and VI (PRO-C6) collagen formation in systemic sclerosis (SSc) patients and examine their correlation to modified Rodnan skin score (mRSS). METHODS: Limited (lSSc, n = 76) and diffuse SSc (dSSc, n = 4...

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OBJECTIVE: The objective was to investigate blood-based biomarkers of type I (PRO-C1), III (PRO-C3) and VI (PRO-C6) collagen formation in systemic sclerosis (SSc) patients and examine their correlation to modified Rodnan skin score (mRSS). METHODS: Limited (lSSc, n = 76) and diffuse SSc (dSSc, n = 4...

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OBJECTIVE: A hallmark of osteoarthritis (OA) is degradation of articular cartilage proteoglycans. In isolated human OA chondrocytes, the anti-inflammatory cytokine Interleukin-37 (IL-37) lowers the expression of the proteolytic MMP and ADAMTS enzymes, which mediate this degradation. Therefore, we in...

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OBJECTIVE: Currently, there are no disease-modifying osteoarthritis drugs (DMOADs) approved for osteoarthritis. It is hypothesized that a subtype of OA may be driven by inflammation and may benefit from treatment with anti-inflammatory small molecule inhibitors adopted from treatments of rheumatoid ...

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BACKGROUND: Radiographic axial spondyloarthritis (r-axSpA) is associated with extracellular matrix (ECM) remodelling of affected tissues. We investigated whether there was a relationship between biomarkers of ECM remodelling and 2-year radiographic progression in r-axSpA. METHODS: Patients from the...

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OBJECTIVES: The expanding spectrum of targeted therapies for rheumatoid arthritis (RA) implies a need for development of precision tools for disease assessment reflecting pathobiologic processes. Type IV collagen is an abundant protein of basement membranes, but is also present in the intercellular ...

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There is a lack of biochemical markers for non-invasive and objective assessment of symptomatic osteoarthritis (OA). Aggrecanase activity has been shown to be associated with joint deterioration and symptomatic disease through the degradation of extracellular matrix proteins, such as type III collag...

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Osteoarthritis (OA) is the most common arthritic disease in the world, leading to debilitating pain and destruction of joint tissues. While pain is the hallmark symptom of osteoarthritis, clear associations between pain and disease processes involved in joint deterioration are lacking. OA pain is mu...

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OBJECTIVE: Rheumatoid arthritis (RA) is a chronic, autoimmune and degenerative joint disease leading to disability, reduced life quality, and increased mortality. Although several synthetic and biological disease modifying anti-rheumatic drugs (DMARDs) are available, there is still a medical need fo...

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Type VII collagen is the main component of the anchoring fibrils connecting the basement membrane to the underlying interstitial matrix. Mutations in the type VII collagen gene cause dystrophic epidermolysis bullosa. Increased levels of type VII collagen in the skin have been reported in patients wi...

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OBJECTIVES: This prospective study aimed to use serological biomarkers for evaluation of, connective tissue turnover, in a population of 149 Japanese patients with rheumatoid arthritis (RA). It was aimed to investigate how the connective tissue was affected by treatment at follow-up after 1 year (+/...

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OBJECTIVES: The objective of this study was to examine the tissue degradation in response to anti-IL6 receptor treatment in rheumatoid arthritis (RA) patients which are anti-TNF-α inadequate responders. METHODS: RADIATE was a randomised, double-blinded, placebo-controlled, parallel-group, phase III...

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Objective Gender is a risk factor in the onset of osteoarthritis (OA). The aim of the study was to investigate gender differences in contact area (CA) and congruity index (CI) in the medial tibiofemoral (MTF) joint in 2 different cohorts, quantified automatically from magnetic resonance imaging (MRI...

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January 9, 2018

Journal:
Cartilage

Author:
Tummala S, Schipdor D, Byrjalsen I, Dam EB

BACKGROUND: Sprifermin (recombinant human fibroblast growth factor 18) is in clinical development as a potential disease-modifying osteoarthritis drug (DMOAD). In vitro studies have shown that cartilage regenerative properties of sprifermin involve chondrocyte proliferation and extracellular matrix ...

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OBJECTIVES:Targeting the granulocyte-macrophage colony-stimulating factor (GM-CSF) pathway holds great potential in the treatment of inflammatory diseases. Mavrilimumab, a human monoclonal GM-CSF receptor-α antibody, has demonstrated clinical efficacy in RA. Our current study aimed to elucidate mech...

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PURPOSE OF REVIEW:There is an increasing demand for noninvasive and descriptive biochemical markers (biomarkers) in osteoarthritis; for enabling early drug development (including translational research), evaluating clinical trial at an early stage and for subtyping. Purpose of the review is to revie...

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Osteoarthritis (OA) is the most common form of joint disease. This presents the OA research community and pharmaceutical companies developing disease-modifying OA drugs (DMOADs) with great opportunities. The different OA subtypes complicate the traditional approaches for developing new treatments. I...

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OBJECTIVE: To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABT-981, a human dual variable domain immunoglobulin simultaneously targeting interleukin (IL)-1α and IL-1β, in patients with knee osteoarthritis (OA). METHOD: This was a randomized, double-blind, placebo-...

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We report the results of a symposium aimed at identifying validated biomarkers that can be used to complement clinical observations for diagnosis and prognosis of joint injury leading to equine osteoarthritis (OA). Biomarkers might also predict pre-fracture change that could lead to catastrophic bon...

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OBJECTIVE: Knee osteoarthritis (OA) is among the higher contributors to global disability. Despite its high prevalence, currently, there is no cure for this disease. Furthermore, the available diagnostic approaches have large precision errors and low sensitivity. Therefore, there is a need for new b...

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The objective of this study was to investigate the patient-reported outcomes (PROs) and matrix metalloproteinase (MMP) derived extracellular matrix (ECM) biomarkers in non-radiographic (nr)-axial spondyloarthritis (axSpA) and radiographic (r)-axSpA after exercise intervention. Forty-six axSpA patien...

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OBJECTIVE: Biologics for rheumatoid arthritis (RA) patients with moderate to severe disease may preserve joint function. Matrix metalloproteinase 3 (MMP-3), a key tissue degrading protease, is highly elevated in RA. MMP-3, which measures the total pool of circulating MMP-3 species (cMMP3), is a comm...

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OBJECTIVE: Fibroblast growth factor (FGF) 18 has been shown to increase cartilage volume when injected intra-articularly in animal models of osteoarthritis (OA) and in patients with knee OA (during clinical development of the recombinant human FGF18, sprifermin). However, the exact nature of this ef...

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OBJECTIVE: To examine the effects of dietary weight loss, with and without exercise, on selected soluble biomarkers in overweight and obese older adults with symptomatic knee osteoarthritis (OA). DESIGN: Blood samples were analyzed from 429 participants in the Intensive Diet and Exercise for Arthri...

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The extracellular matrix (ECM) of articular cartilage is comprised of complex networks of proteins and glycoproteins, all of which are expressed by its resident cell, the chondrocyte. Cartilage is a unique tissue given its complexity and ability to resist repeated load and deformation. The mechanism...

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Articular cartilage is a connective tissue consisting of a specialized extracellular matrix (ECM) that dominates the bulk of its wet and dry weight. Type II collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, es...

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PURPOSE: The aim of this \"Year in Review\" article is to summarize and discuss the implications of biochemical marker related articles published between the Osteoarthritis Research Society International (OARSI) 2015 Congress in Seattle and the OARSI 2016 Congress in Amsterdam. METHODS: The PubMed/...

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