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Rheumatology, Osteoarthritis
7. Sep 2018

IL-37 diminishes proteoglycan loiss in human OA cartilage: donor-specific link between IL-37 and MMP-3.

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 i…

Rheumatology, Osteoarthritis
29. Jul 2018

Tofacitinib and TPCA-1 Exert Chondroprotective Effects on Extracellular Matrix Turnover in Bovine Articular Cartilage Ex vivo.

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…

Rheumatology, Osteoarthritis
25. Apr 2018

Protein biomarkers associated with pain mechanisms in osteoarthritis

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…

Rheumatology, Osteoarthritis, Extracellular Matrix Research
25. Apr 2018

Aggrecanase degradation of type III collagen is associated with clinical knee pain

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…

Bone, Extracellular Matrix Research, Osteoarthritis
10. Apr 2018

Osteoclasts degrade bone and cartilage knee joint compartments through different resorption processes

BACKGROUND:
Osteoclasts have been strongly implicated in osteoarthritic cartilage degradation, at least indirectly via bone resorption, and have been shown to degrade cartilage in vitro. The osteoclast resorption processes required to degrade subchondral bone and cartilage-the remodeling of which i…

Osteoarthritis
17. Jan 2018

Identification of pain categories associated with change in pain in patients receiving placebo: Data from Two Phase 3 Randomized Clinical Trials in Symptomatic Knee Osteoarthritis

BACKGROUND:
Pain is the principal clinical symptom of osteoarthritis (OA), and development of safe and effective analgesics for OA pain is needed. Drug development of new analgesics for OA pain is impaired by substantial change in pain in patients receiving placebo, and more data describing clinica…

Rheumatology, Osteoarthritis, Clinical Data Quality
9. Jan 2018

Gender Differences in Knee Joint Congruity Quantified from MRI: A Validation Study with Data from Center for Clinical and Basic Research and Osteoarthritis Initiative.

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…

Rheumatology, Osteoarthritis
12. Dec 2017

Sprifermin (rhFGF18) Modulates Extracellular Matrix Turnover in Cartilage Explants ex vivo

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…

Rheumatology, Osteoarthritis
16. Oct 2017

Development and use of biochemical markers in osteoarthritis: current update

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 rev…

Rheumatology, Osteoarthritis
14. Oct 2017

Biochemical marker discovery, testing and evaluation for facilitating OA drug discovery and development

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…

Rheumatology, Osteoarthritis
28. Sep 2017

Safety, Tolerability, and Pharmacodynamics of an Anti-Interleukin-1 α/β Dual Variable Domain Immunoglobulin in Patients With Osteoarthritis of the Knee: A Randomized Phase 1 Study

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, plac…

Rheumatology, Osteoarthritis
16. Sep 2017

Biomarkers for equine joint injury and osteoarthritis

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…

Rheumatology, Osteoarthritis, Obesity
9. Sep 2017

A machine learning approach for the identification of new biomarkers for knee osteoarthritis development in overweight and obese women

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 …

Rheumatology, Osteoarthritis
18. Aug 2017

Sprifermin (rhFGF18) enables proliferation of chondrocytes producing a hyaline cartilage matrix

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 e…

Obesity, Rheumatology, Osteoarthritis
27. Jul 2017

Effects of dietary weight loss with and without exercise on interstitial matrix turnover and tissue inflammation biomarkers in adults with knee osteoarthritis: the Intensive Diet and Exercise for Arthritis trial (IDEA)

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 Ar…

Extracellular Matrix Research, Osteoarthritis
22. Mar 2017

Biomarker of extracellular matrix remodelling C1M and proinflammatory cytokine IL-6 are related to synovitis and pain in endstage knee osteoarthritis patients

Little is known about local and systemic biomarkers in relation to synovitis and pain in end-stage osteoarthritis (OA) patients. We investigated the associations between the novel extracellular matrix biomarker, C1M, and local and systemic interleukin 6 (IL-6) with synovitis and pain. Serum C1M, pla…

Osteoarthritis, Rheumatology, Extracellular Matrix Research
20. Feb 2017

Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis

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…

Osteoarthritis
20. Jan 2017

Identification of serological biomarker profiles associated with total joint replacement in osteoarthritis patients

OBJECTIVE:
Establish a biomarker panel associated with all-cause total joint replacement (TJR) through identification of patients with osteoarthritis (OA) who do or do not progress to TJR and investigate effects of nonsteroidal anti-inflammatory drugs (NSAIDs).

DESIGN:
Serum samples from patien…

Rheumatology, Osteoarthritis
16. Jan 2017

Osteoarthritis Year in Review 2016: biomarkers (biochemical markers)

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 PubMe…

Rheumatology, Osteoarthritis
11. Oct 2016

The association between histological, macroscopic and magnetic resonance imaging assessed synovitis in end-stage knee osteoarthritis: a cross-sectional study

OBJECTIVES:
To investigate the association between magnetic resonance imaging (MRI), macroscopic and histological assessments of synovitis in end-stage knee osteoarthritis (KOA).

METHODS:
Synovitis of end-stage osteoarthritic knees was assessed using non-contrast-enhanced (CE), contrast-enhance…

Rheumatology, Osteoarthritis
2. Aug 2016

Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future

Osteoarthritis (OA) is the biggest unmet medical need among the many musculoskeletal conditions and the most common form of arthritis. It is a major cause of disability and impaired quality of life in the elderly. We review several ambitious but failed attempts to develop joint structure-modifying t…

Rheumatology, Osteoarthritis
5. May 2016

The Need for Predictive, Prognostic, Objective and Complementary Blood-Based Biomarkers in Osteoarthritis (OA)

Osteoarthritis (OA) has traditionally been viewed as a non-inflammatory arthropathy and has not been considered a ‘serious disease’. However, this view has radically changed in recent years, due to the complexity and heterogeneity of the patient populations, spiralling socio-economical costs and lon…

Rheumatology, Osteoarthritis
28. Apr 2016

Osteoarthritis biomarkers derived from cartilage extracellular matrix: Current status and future perspectives

Specific soluble biomarkers can be powerful tools for the diagnosis, prognosis and personalized management of osteoarthritis (OA). Biomarkers are potential indicators of the effect of a drug on cartilage metabolism and provide crucial information about the mechanisms of drug action. In this review, …

Rheumatology, Osteoarthritis
1. Apr 2016

Association between biomarkers of tissue inflammation and progression of osteoarthritis: evidence from the Rotterdam study cohort

BACKGROUND:
We aimed to investigate the prognostic value of two biomarkers of tissue inflammation, matrix metalloproteinase-dependent degradation of C-reactive protein (CRPM) and connective tissue type I collagen turnover (C1M), on the incidence and progression of radiographic osteoarthritis (OA) i…

Rheumatology, Osteoarthritis, Extracellular Matrix Research
10. Feb 2016

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

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 …

Rheumatology, Osteoarthritis
25. Jan 2016

Osteoarthritis year in review 2015: soluble biomarkers and the BIPED criteria

OBJECTIVE:
To review and summarize biomarker data published from April 2014 to May 2015 to provide insight to the ongoing work in the field of osteoarthritis (OA). Furthermore, to summarize the BIPED criteria and set it in context of the medical needs of 2015.

METHODS:
PubMed was used as search…

Rheumatology, Osteoarthritis
21. Dec 2015

Serum cartilage oligomeric matrix protein and development of radiographic and painful knee osteoarthritis. A community-based cohort of middle-aged women

CONTEXT AND OBJECTIVE:
We evaluated the predictive value of serum cartilage oligomeric matrix protein (sCOMP) levels over 20 years on the development of radiographic (RKOA) and painful knee osteoarthritis (KOA) in a longitudinal cohort of middle-aged women.

MATERIALS AND METHODS:
Five hundred a…

Rheumatology, Osteoarthritis
2. Dec 2015

Sensitization and Serological Biomarkers in Knee Osteoarthritis Patients With Different Degrees of Synovitis

OBJECTIVE:
Synovitis is a frequent condition in knee osteoarthritis (KOA) and has been associated with pain. This study investigated the links between the pressure hyperalgesia, the clinical pain, the degree of the synovitis, inflammatory biomarkers, and tissue-specific biomarkers in KOA patients. …

Rheumatology, Osteoarthritis
20. Oct 2015

Inflammation (or synovitis)-driven osteoarthritis: an opportunity for personalizing prognosis and treatment?

The disabling and painful disease osteoarthritis (OA) is the most common form of arthritis. Strong evidence suggests that a subpopulation of OA patients has a form of OA driven by inflammation. Consequently, understanding when inflammation is the driver of disease progression and which OA patients m…

Rheumatology, Osteoarthritis
1. Aug 2015

Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use

Osteoarthritis (OA) is a heterogeneous disorder. The goals of this review are (1) To stimulate use of standardized nomenclature for OA that could serve as building blocks for describing OA and defining OA phenotypes, in short to provide unifying disease concepts for a heterogeneous disorder; and (2)…

Rheumatology, Osteoarthritis
24. Apr 2015

The effect of protease inhibitors on the induction of osteoarthritis-related biomarkers in bovine full-depth cartilage explants

OBJECTIVE:
The specific degradation of type II collagen and aggrecan by matrix metalloproteinase (MMP)-9, -13 and ADAMTS-4 and -5 (aggrecanase-1 and -2) in the cartilage matrix is a critical step in pathology of osteoarthritis (OA). The aims of this study were: i) To investigate the relative contri…

Rheumatology, Osteoarthritis
1. Apr 2015

OA phenotypes, rather than disease stage, drive structural progression--identification of structural progressors from 2 phase III randomized clinical studies with symptomatic knee OA

BACKGROUND/PURPOSE:
The aim of this study was to identify key characteristics of disease progression through investigation of the association of radiographic progression over two years with baseline Joint Space Width (JSW), Kellgren-Lawrence (KL) grade, Western Ontario and McMaster Universities Art…

Rheumatology, Osteoarthritis
1. Apr 2015

Treatment of symptomatic knee osteoarthritis with oral salmon calcitonin: results from two phase 3 trials

PURPOSE:
To evaluate the structure-modifying and symptom efficacy, as well as safety and tolerability of oral salmon calcitonin (sCT) formulated with a 5-CNAC carrier (a molecule based on Eligen(®) technology), in osteoarthritis (OA) patients with moderate to severe knee pain and joint structural d…

Rheumatology, Osteoarthritis
1. Jan 2015

Association between biochemical cartilage markers and clinical symptoms in patients with hip osteoarthritis: cohort study with 2-year follow-up

OBJECTIVES:
To assess associations between uCTX-II or uCIIM and severity of hip pain in patients with mild-moderate hip osteoarthritis (OA) over a 2-year period, and establish whether the level of these biomarkers at baseline could estimate a specific trajectory of hip pain.

DESIGN:
A cohort st…

Rheumatology, Osteoarthritis
1. Jan 2015

Identifying specific profiles in patients with different degrees of painful knee osteoarthritis based on serological biochemical and mechanistic pain biomarkers: a diagnostic approach based on cluster analysis

Biochemical and pain biomarkers can be applied to patients with painful osteoarthritis profiles and may provide more details compared with conventional clinical tools. The aim of this study was to identify an optimal combination of biochemical and pain biomarkers for classification of patients with …

Rheumatology, Osteoarthritis
11. Dec 2014

Association between experimental pain biomarkers and serologic markers in patients with different degrees of painful knee osteoarthritis

OBJECTIVE:
To assess the association between pain mechanisms (sensitization) and biochemical markers for cartilage, bone, and inflammation in patients with knee pain.

METHODS:
The study group comprised 281 patients with different degrees of knee pain intensity and radiographic findings (using t…

Rheumatology, Osteoarthritis
4. Dec 2014

Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment

BACKGROUND:
Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied.

METHOD…

Osteoarthritis, Rheumatology
17. Oct 2014

Cartilage turnover reflected by metabolic processing of type II collagen: a novel marker of anabolic function in chondrocytes

The aim of this study was to enable measurement of cartilage formation by a novel biomarker of type II collagen formation. The competitive enzyme-linked immunosorbent assay (ELISA) Pro-C2 was developed and characterized for assessment of the beta splice variant of type II procollagen (PIIBNP). This …

Osteoarthritis
1. Sep 2014

Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis

OBJECTIVE:
To evaluate joint tissue remodeling using the urinary collagen biomarkers urinary α-C-telopeptide of type I collagen (α-CTX) and urinary C-telopeptide of type II collagen (CTX-II) and to determine the association of these biomarkers with osteoarthritis (OA) severity, progression, and loc…

Rheumatology, Osteoarthritis
28. Aug 2014

Association Between Experimental Pain Biomarkers and Serological Markers in Patients With Different Degree of Painful Knee Osteoarthritis

OBJECTIVE:
To assess the association between pain mechanisms (sensitization) and biochemical markers for cartilage, bone, and inflammation in patients with knee pain.

METHODS:
The study group comprised 281 patients with different degrees of knee pain intensity and radiographic findings (using t…

Rheumatology, Osteoarthritis
1. Aug 2014

Biomarkers of cartilage and surrounding joint tissue

The identification and clinical demonstration of efficacy and safety of osteo- and chondro-protective drugs are met with certain difficulties. During the last few decades, the pharmaceutical industry has, in the field of rheumatology, experienced disappointments associated with the development of di…

Rheumatology, Osteoarthritis
23. Jul 2014

Meta-analysis identifies loci affecting levels of the potential osteoarthritis biomarkers sCOMP and uCTX-II with genome wide significance

BACKGROUND:
Research for the use of biomarkers in osteoarthritis (OA) is promising, however, adequate discrimination between patients and controls may be hampered due to innate differences. We set out to identify loci influencing levels of serum cartilage oligomeric protein (sCOMP) and urinary C-te…

Bone, Rheumatology, Osteoarthritis
6. Jun 2014

ALPHA-CTX is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis

OBJECTIVE:
To evaluate joint tissue remodeling, with urinary collagen biomarkers, uALPHA CTX and uCTXII, and their association with osteoarthritis (OA) severity, progression, and localized knee bone turnover.

METHODS:
Participants (N=149) with symptomatic and radiographic knee OA underwent fixe…

Osteoarthritis
22. May 2014

Large scale meta-analysis of urinary C-terminal telopeptide, serum cartilage oligomeric protein and matrix metalloprotease degraded type II collagen and their role in prevalence, incidence and progression of osteoarthritis

OBJECTIVE:
To evaluate the role of three cartilage-derived biomarkers on osteoarthritis (OA): urinary C-terminal telopeptide (uCTX-II), serum cartilage oligomeric protein (sCOMP), and serum MMP degraded type II collagen (sC2M).

SUBJECTS AND METHODS:
Samples from 3582 individuals from the Rotter…

Osteoarthritis
19. Mar 2014

The active form of MMP-3 is a marker of synovial inflammation and cartilage turnover in inflammatory joint diseases

BACKGROUND:
Matrix metalloproteinase-3 (MMP-3) plays an important role in the pathology of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Measurement of active MMP-3 in clinical samples could provide information about progression of rheumatoid diseases, and potentially response to treat…

Rheumatology, Osteoarthritis
1. Mar 2014

Republished: Value of biomarkers in osteoarthritis: current status and perspectives

Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of t…

Rheumatology, Osteoarthritis
6. Feb 2014

The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments?

Osteoarthritis (OA) is the most common form of arthritic disease, and a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, affecting bone, cartilage and synovium that thereby presents multiple targets for treatment. This manuscript wil…

Rheumatology, Osteoarthritis
22. Jan 2014

Osteoarthritis--a case for personalized health care?

For both economic and ethical reasons, identification of the optimal treatment for each individual patient is a pressing concern, not only for the patients and their physician, but also health care payers and the pharmaceutical industry. In the field of osteoarthritis (OA) this is of particular rele…

Rheumatology, Osteoarthritis
7. Jan 2014

Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover

OBJECTIVES:
Osteoarthritis (OA) is a degenerative disease with a subset of patients experiencing joint inflammation, but C-reactive protein (CRP) has shown limited use in OA as a diagnostic marker. The aim was to identify subpopulations of patients with high or low levels of acute (high sensitive C…

Rheumatology, Osteoarthritis
12. Nov 2013

Value of biomarkers in osteoarthritis: current status and perspectives

Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of t…

Rheumatology, Osteoarthritis
17. Oct 2013

Metabolic health in families enriched for longevity is associated with low prevalence of hand osteoarthritis and influences OA biomarker profiles

OBJECTIVES:
Individual metabolic characteristics and age-related changes may affect osteoarthritis (OA) risk as well as levels of potential OA biomarkers such as serum cartilage oligomeric protein (sCOMP) and urinary cross-linked C-telopeptide of type 2 collagen (uCTX2). We investigated hand OA and…

Rheumatology, Osteoarthritis
6. Oct 2013

The development and characterization of an ELISA specifically detecting the active form of cathepsin K

OBJECTIVE:
Cathepsin K plays essential roles in bone resorption and is intensely investigated as a therapeutic target for the treatment of osteoporosis. Hence an assessment of the active form of cathepsin K may provide important biological information in metabolic bone diseases, such as osteoporosi…

Rheumatology, Osteoarthritis
14. Aug 2013

Serological identification of fast progressors of structural damage with rheumatoid arthritis

INTRODUCTION:
Rheumatoid arthritis (RA) patients with structural progression are in most need of immediate treatment to maintain tissue integrity. The serum protein fingerprint, type I collagen degradation mediated by matrix metalloproteinases (MMP)-cleavage (C1M), is a biomarker of tissue destruct…

Rheumatology, Osteoarthritis
13. May 2013

Role of hormones in cartilage and joint metabolism: understanding an unhealthy metabolic phenotype in osteoarthritis

OBJECTIVE:
Joint health is affected by local and systemic hormones. It is well accepted that systemic factors regulate the metabolism of joint tissues, and that substantial cross-talk between tissues actively contributes to homeostasis. In the current review, we try to define a subtype of osteoarth…

Rheumatology, Osteoarthritis
24. Apr 2013

The development and characterization of a competitive ELISA for measuring active ADAMTS-4 in a bovine cartilage ex vivo model

ADAMTS-4 (aggrecanase1) is believed to play an important role in the degradation of aggrecan during the progression of joint diseases. ADAMTS-4 is synthesized as a latent pro-enzyme that requires the removal of the pro-domain, exposing the N-terminal neoepitope, to achieve activity. We developed a m…

Rheumatology, Osteoarthritis
14. Feb 2013

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

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 incl…

Rheumatology, Osteoarthritis
3. Jan 2013

Bringing cancer serological diagnosis to a new level: focusing on HER2, protein ectodomain shedding and neoepitope technology

Cancer is a heterogeneous disease and consequently an exact diagnosis is as important as the actual therapy. Therefore, identification of novel diagnostic biomarker targets is urgently needed. Physiological and pathological changes are reflected by post-translational modifications of proteins. Each …

Rheumatology, Osteoarthritis
18. Dec 2012

The pathogenesis of osteoarthritis involves bone, cartilage and synovial inflammation: may estrogen be a magic bullet?

The female predominance of polyarticular osteoarthritis (OA), and in particular the marked increase of OA in women after the menopause points to a likely involvement of female sex hormones in the maintenance of cartilage homeostasis. This perception has inspired many research groups to investigate t…

Rheumatology, Osteoarthritis
1. Jul 2012

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

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. W…

Rheumatology, Osteoarthritis
15. Feb 2012

Mice over-expressing salmon calcitonin have strongly attenuated osteoarthritic histopathological changes after destabilization of the medial meniscus

OBJECTIVE:
Calcitonin is well-known for its inhibitory actions on bone-resorbing osteoclasts and recently potential beneficial effects on cartilage were shown. We investigated effects of salmon calcitonin (sCT) on the articular cartilage and bone, after destabilization of the medial meniscus (DMM) …

Rheumatology, Osteoarthritis
18. Jan 2012

The distribution pattern of critically short telomeres in human osteoarthritic knees

INTRODUCTION
Telomere shortening is associated with a number of common age-related diseases. A role of telomere shortening in osteoarthritis (OA) has been suggested, mainly based on the assessment of mean telomere length in ex vivo expanded chondrocytes. We addressed this role directly in vivo by u…

Rheumatology, Osteoarthritis, Rheumatoid Arthritis
8. Dec 2011

Molecular serum and urine marker repertoire supporting clinical research on joint diseases

The need for improved analytical techniques in the study of slow, degenerative diseases such as rheumatoid arthritis and osteoarthritis has driven major efforts aimed at identifying biochemical markers of pathological processes in both diseases. A series of novel biochemical markers has surfaced and…

Rheumatology, Osteoarthritis
13. Oct 2011

Identification of the calcitonin receptor in osteoarthritic chondrocytes

BACKGROUND:
Preclinical and clinical studies have shown that salmon calcitonin has cartilage protective effects in joint degenerative diseases, such as osteoarthritis (OA). However, the presence of the calcitonin receptor (CTR) in articular cartilage chondrocytes is yet to be identified. In this st…

Rheumatology, Osteoarthritis
14. Jul 2011

Characterization of an Ex vivo Femoral Head Model Assessed by Markers of Bone and Cartilage Turnover

OBJECTIVE:
The pathophysiology of osteoarthritis involves the whole joint and is characterized by cartilage degradation and altered subchondral bone turnover. At present, there is a need for biological models that allow investigation of the interactions between the key cellular players in bone/cart…

Rheumatology, Osteoarthritis
19. Apr 2011

Oral salmon calcitonin reduces cartilage and bone pathology in an osteoarthritis rat model with increased subchondral bone turnover

OBJECTIVES:
Traumatic osteoarthritis (OA) is possibly augmented by effects from loss of sex hormones. Salmon calcitonin is shown to reduce OA pathogenesis and bone resorption. We investigated the effects of oral salmon calcitonin treatment and ovariectomy on cartilage and bone pathology in a trauma…

Rheumatology, Osteoarthritis
13. Apr 2011

Enzyme-linked immunosorbent assay (ELISAs) for metalloproteinase derived type II collagen neoepitope, CIIM--increased serum CIIM in subjects with severe radiographic osteoarthritis

OBJECTIVES:
In joint degenerative diseases, the collagens are degraded by matrix metalloproteinases and protein fragments are released to serum as potential biomarkers.

METHODS:
A collagen type II specific neoepitope, CIIM, was identified (…RDGAAG(1053)) by mass spectrometry. Two ELISAs against…

Rheumatology, Osteoarthritis
15. Mar 2011

A microarray analysis of full depth knee cartilage of ovariectomized rats

BACKGROUND:
This short communication focuses the on articular cartilage and the subchondral bone, both of which play important roles in the development of osteoarthritis (OA). There are indications that estrogen-deficiency, as the post-menopausal state, accelerate the development of OA.

FINDINGS…

Rheumatology, Osteoarthritis
3. Jan 2011

Tummala SDiagnosis of Osteoarthritis by Cartilage Surface Smoothness Quantified Automatically from Knee MRI

OBJECTIVE:
We investigated whether surface smoothness of articular cartilage in the medial tibiofemoral compartment quantified from magnetic resonance imaging (MRI) could be appropriate as a diagnostic marker of osteoarthritis (OA).

METHOD:
At baseline, 159 community-based subjects aged 21 to 8…

Rheumatology, Osteoarthritis
17. Jun 2010

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

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 In…

Rheumatology, Osteoarthritis
15. May 2010

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

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 profil…

Rheumatology, Osteoarthritis
5. Apr 2010

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

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 proteogly…

Rheumatology, Osteoarthritis
28. Feb 2010

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

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 join…

Rheumatology, Osteoarthritis
15. Feb 2010

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

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…

Rheumatology, Osteoarthritis
2. Feb 2010

Biglycan and fibromodulin have essential roles in regulating chondrogenesis and extracellular matrix turnover in temporomandibular joint osteoarthritis

The temporomandibular joint is critical for jaw movements and allows for mastication, digestion of food, and speech. Temporomandibular joint osteoarthritis is a degenerative disease that is marked by permanent cartilage destruction and loss of extracellular matrix (ECM). To understand how the ECM re…

Rheumatology, Osteoarthritis
18. Dec 2009

Suppression of MMP activity in bovine cartilage explants cultures has little if any effect on the release of aggrecanase-derived aggrecan fragments

Progressive loss of articular cartilage is a central hallmark in many joint disease, however, the relative importance of individual proteolytic pathways leading to cartilage erosion is at present unknown. We therefore investigated the time-dependant release ex vivo of MMP- and aggrecanase-derived fr…

Rheumatology, Osteoarthritis
24. Jul 2009

Identification of progressors in osteoarthritis by combining biochemical and MRI-based markers

INTRODUCTION:
At present, no disease-modifying osteoarthritis drugs (DMOADS) are approved by the FDA (US Food and Drug Administration); possibly partly due to inadequate trial design since efficacy demonstration requires disease progression in the placebo group. We investigated whether combinations…

Rheumatology, Osteoarthritis
15. Jun 2009

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

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 cartila…

Rheumatology, Osteoarthritis
31. Aug 2008

Characterization of metalloprotease cleavage products of human articular cartilage

OBJECTIVE:
To identify, characterize, and compare proteolysis peptide products generated by metalloprotease digests of human articular cartilage.

METHODS:
Human articular cartilage was digested by the addition of exogenous metalloproteases, including matrix metalloproteinases 2, 3, 8, 9, 12, an…

Rheumatology, Osteoarthritis
16. Jun 2008

Should subchondral bone turnover be targeted when treating osteoarthritis?

OBJECTIVE:
Osteoarthritis (OA) is the most common form of arthritic disease, and it is a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, including bone and cartilage, thereby presenting alternative approaches for treatment. This re…

Rheumatology, Osteoarthritis
6. Jun 2008

Automatic quantification of local and global articular cartilage surface curvature: biomarkers for osteoarthritis

The objective of this study was to quantitatively assess the surface curvature of the articular cartilage from low-field magnetic resonance imaging (MRI) data, and to investigate its role in populations with varying radiographic signs of osteoarthritis (OA), cross-sectionally and longitudinally. The…

Rheumatology, Osteoarthritis
8. May 2008

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

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 c…

Rheumatology, Osteoarthritis
10. Apr 2008

Oestrogen exhibits type II collagen protective effects and attenuates collagen-induced arthritis in rats

As anti-inflammatory treatments used in rheumatoid arthritis, such as glucocorticoids, often result in secondary detrimental effects on bone health, the objective of this study was to investigate the effects of oestrogen therapy (ET) on the development and activity of collagen-induced arthritis (CIA…

Rheumatology, Osteoarthritis
13. Feb 2008

Evaluation of cartilage damage by measuring collagen degradation products in joint extracts in a traumatic model of osteoarthritis

The objective of this work was to investigate whether collagen degradation products in protein extract from joints could provide quantitative information on cartilage damage. Osteoarthritis (OA) was surgically induced in rat knee joints. Joints were isolated 7, 14 and 28 days after surgery for prote…

Rheumatology, Osteoarthritis
11. Feb 2008

An update review of cellular mechanisms conferring the indirect and direct effects of estrogen on articular cartilage

OBJECTIVE:
To review cellular mechanisms that have been proposed to mediate the indirect and direct effects of estrogen on articular cartilage, and to outline the remaining clinical questions that need to be clarified before utilizing the beneficial effects of estrogen for the prevention of osteoar…

Rheumatology, Osteoarthritis
7. Nov 2007

Calcitonin affects both bone and cartilage: a dual action treatment for osteoarthritis?

Osteoarthritis (OA) is the most common form of degenerative joint diseases and a major cause of disability and impaired quality of life in the elderly. OA is a complex disease involving both bone and cartilage properties, and may therefore require alternative approaches for treatment. Recent lines o…

Rheumatology, Osteoarthritis
14. Oct 2007

Osteoarthritic cartilage is more homogeneous than healthy cartilage: identification of a superior region of interest colocalized with a major risk factor for osteoarthritis

RATIONALE AND OBJECTIVES:
Cartilage loss as determined by magnetic resonance imaging (MRI) or joint space narrowing as determined by x-ray is the result of cartilage erosion. However, metabolic processes within the cartilage that later result in cartilage loss may be a more sensitive assessment met…

Rheumatology, Osteoarthritis
15. Aug 2007

The effect of oral calcitonin on cartilage turnover and surface erosion in an ovariectomized rat model

OBJECTIVE:
To investigate whether oral calcitonin treatment influences the increases in type II collagen (CII) degradation and related surface erosions of articular cartilage in ovariectomized rats.

METHODS:
Fifty rats were randomly allocated into 1 of the 5 following intervention groups: sham-…

Rheumatology, Osteoarthritis
10. Aug 2007

Bone, cartilage and hormone therapy: established concepts and future scenarios

In the aftermath of the Women's Health Initiative (WHI) study, the firm ground of postmenopausal hormone therapy (HT) has been thoroughly shaken. While there was agreement that HT is indicated for the therapy of menopause-associated vasomotor symptoms and vulvovaginal atrophy, there was a general an…

Rheumatology, Osteoarthritis
20. May 2007

Induction of increased cAMP levels in articular chondrocytes blocks matrix metalloproteinase-mediated cartilage degradation, but not aggrecanase-mediated cartilage degradation

OBJECTIVE:
Calcitonin has been suggested to have chondroprotective effects. One signaling pathway of calcitonin is via the second messenger cAMP. We undertook this study to investigate whether increased cAMP levels in chondrocytes would be chondroprotective.

METHODS:
Cartilage degradation was i…

Rheumatology, Osteoarthritis
10. May 2007

Separation of healthy and early osteoarthritis by automatic quantification of cartilage homogeneity

OBJECTIVE:
Cartilage loss as determined either by magnetic resonance imaging (MRI) or by joint space narrowing in X-rays is the result of cartilage erosion. However, metabolic processes within the cartilage that later result in cartilage loss may be a more accurate assessment method for early chang…

Rheumatology, Osteoarthritis
15. Mar 2007

Anabolic and catabolic function of chondrocyte ex vivo is reflected by the metabolic processing of type II collagen

The aim of the present study was to investigate collagen metabolism after anabolic and catabolic stimulation of chondrocytes ex vivo.

DESIGN:
Metabolic activities in ex vivo bovine cartilage explants were stimulated with insulin-like growth factor I (IGF-I) or a combination of tumor necrosis fac…

Rheumatology, Osteoarthritis
15. Feb 2007

MMP and non-MMP-mediated release of aggrecan and its fragments from articular cartilage: a comparative study of three different aggrecan and glycosaminoglycan assays

Aggrecan is the major proteoglycan in articular cartilage and is known to be degraded by various proteases, including matrix metalloproteinases (MMPs). The present study was undertaken to develop immunoassays detecting aggrecan and its fragments generated by MMP and non-MMP-mediated proteolysis.

Rheumatology, Osteoarthritis
14. Aug 2006

Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes

OBJECTIVE:
Calcitonin was recently reported to counter progression of cartilage degradation in an experimental model of osteoarthritis, and the effects were primarily suggested to be mediated by inhibition of subchondral bone resorption. We investigated direct effects of calcitonin on chondrocytes …

Rheumatology, Osteoarthritis
3. Aug 2006

Effects of ovariectomy and estrogen therapy on type II collagen degradation and structural integrity of articular cartilage in rats: implications of the time of initiation

OBJECTIVE:
To investigate how the time of initiation influences the effects of estrogen therapy on type II collagen (CII) turnover and the structural integrity of articular cartilage in ovariectomized rats and to determine whether estrogen exerts direct effects on the catabolic function of chondroc…

Rheumatology, Osteoarthritis
14. Jul 2006

Calcitonin is involved in cartilage homeostasis: is calcitonin a treatment for OA?

OBJECTIVE:
Osteoarthritis (OA) is the most common form of degenerative joint diseases and a major cause of disability and impaired quality of life in the elderly. Recent observations suggest that calcitonin may act on both osteoclasts and chondrocytes. The present review was sought to summarize eme…

Rheumatology, Osteoarthritis
14. Jul 2006

The utility of measuring C-terminal telopeptides of collagen type II (CTX-II) in serum and synovial fluid samples for estimation of articular cartilage status in experimental models of destructive joint diseases

OBJECTIVE:
To characterize and validate a novel, enzyme-linked immunoassay for measuring cross-linked dimer forms of C-terminal telopeptides of type II collagen (CTX-II) in serum and synovial fluid of rodents, and investigate whether CTX-II measurements can reflect joint status in two established a…

Rheumatology, Osteoarthritis
23. Mar 2006

Relative contribution of matrix metalloprotease and cysteine protease activities to cytokine-stimulated articular cartilage degradation

OBJECTIVE:
Both matrix metalloprotease (MMP) activity and cathepsin K (CK) activity have been implicated in cartilage turnover. We investigated the relative contribution of MMP activity and CK activity in cartilage degradation using ex vivo and in vivo models.

METHODS:
Bovine articular cartilag…

Rheumatology, Osteoarthritis
7. Jul 2005

Oral salmon calcitonin induced suppression of urinary collagen type II degradation in postmenopausal women: a new potential treatment of osteoarthritis

OBJECTIVE:
To assess the efficacy of 3 months of oral salmon calcitonin (sCT) on cartilage degradation as estimated by the changes in the urinary excretion of C-terminal telopeptide of collagen type II (CTX-II), and to investigate whether the response of oral sCT to urinary CTX-II depends on the ba…

Rheumatology, Osteoarthritis
1. Jul 2005

The clinical potential of estrogen for the prevention of osteoarthritis: what is known and what needs to be done?

Osteoarthritis (OA) remains a major epidemiological problem worldwide. The lack of established chondroprotective agents limits the clinical management of this disease to relief of symptoms, such as pain and joint stiffness. The marked increase in the prevalence and incidence of OA among women after …