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...
Background: Excessive cartilage degradation is a known characteristic of osteoarthritis (OA). Biochemical markers, such as uCTX-II, have been shown to be associated with disease severity, yet the tissue origin of CTX-II has been disputed. This analysis investigates the association between OA knee jo...
September 3, 2019
Journal:
Arthritis Res Ther
Author:
Bihlet AR, Byrjalsen I, Bay-Jensen AC, Andersen JR, Christiansen C, Riis BJ, Karsdal MA
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...
September 7, 2018
Journal:
Osteoarthritis Cartilage
Author:
Van Geffen EW, Van Caam APM, Van de Loo FA, Van Lent PLEM, Koenders MI, Thudium CS, Bay-Jensen AC, Blaney Davidson EN, Van der Kraan PM
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 ...
July 29, 2018
Journal:
Biochem Pharmacol
Author:
Kjelgaard-Petersen CF, Sharma N, Kayed A, Karsdal MA, Mobasheri A, Hägglund P, Bay-Jensen AC, Thudium CS
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...
April 25, 2018
Journal:
Clin Biochem
Author:
Bay-Jensen AC, Kjelgaard-Petersen CF, Petersen KK, Arendt-Nielsen L, Quasnichka HL, Mobasheri A, Karsdal MA, Leeming DJ
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...
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 is...
April 10, 2018
Journal:
Arthritis Res Ther
Author:
Löfvall H, Newbould H, Karsdal MA, Dziegiel MH, Richter J, Henriksen K, Thudium CS
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 clinical...
January 17, 2018
Journal:
BMC Musculoskelet Disord
Author:
Bihlet AR, Byrjalsen I, Bay-Jensen AC, Andersen JR, Christiansen C, Riis BJ, Valter I, Karsdal MA, Hochberg MC
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...
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 ...
December 12, 2017
Journal:
J Transl Med
Author:
Reker D, Kjelgaard-Petersen CF, Siebuhr AS, Michaelis M, Gigout A, Karsdal MA, Ladel C, Bay-Jensen AC
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...
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...
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-...
September 28, 2017
Journal:
Osteoarthritis Cartilage
Author:
Wang SX, Abramson SB, Attur M, Karsdal MA, Preston RA, Lozada CJ, Kosloski MP, Hong F, Jiang P, Saltarelli MJ, Hendrickson BA, Medema JK
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...
September 16, 2017
Journal:
J Orthop Res.
Author:
McIlwraith CW, Kawcak CE, Frisbie DD, Little CB, Clegg PD, Peffers MJ, Karsdal MA, Ekman S, Laverty S, Slayden RA, Sandell LJ, Lohmander LS, Kraus VB
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...
September 9, 2017
Journal:
Osteoarthritis Cartilage
Author:
Bacardit J, Henrotin Y, Bierma-Zeinstra SMA, Thudium CS, Bay-Jensen AC, Runhaar J, Lazzarini N
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...
August 18, 2017
Journal:
Osteoarthritis Cartilage
Author:
Gigout A, Guehring H, Froemel D, Meurer A, Ladel C, Reker D, Bay-Jensen AC, Karsdal MA, Lindemann S
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...
July 27, 2017
Journal:
Osteoarthritis Cartilage
Author:
Loeser RF, Beavers DP, Bay-Jensen AC, Karsdal MA, Nicklas BJ, Guermazi A, Hunter DJ, Messier SP
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...
February 20, 2017
Journal:
Osteoarthritis Cartilage
Author:
Sanchez C, Bay-Jensen AC, Pap T, Dvir-Ginzberg M, Quasnichka H, Barrett-Jolley R, Mobasheri A, Henrotin Y
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/...
January 16, 2017
Journal:
Osteoarthritis Cartilage
Author:
Mobasheri A, Bay-Jensen AC, Van Spil WE, Larkin J, Levesque MC
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-enhanced ma...
October 11, 2016
Journal:
Osteoarthritis Cartilage
Author:
Riis RG, Gudbergsen H, Simonsen O, Henriksen M, Al-Mashkur N, Eld M, Petersen KK, Kubassova O, Bay Jensen AC, Damm J, Bliddal H, Arendt-Nielsen L, Boesen MP
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...
August 2, 2016
Journal:
Osteoarthritis Cartilage
Author:
Karsdal MA, Michaelis M, Ladel C, Siebuhr AS, Bihlet AR, Andersen JR, Guehring H, Christiansen C, Bay-Jensen AC, Kraus VB
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...
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, ...
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) in...
April 1, 2016
Journal:
Arthritis Res Ther
Author:
Saberi Hosnijeh F, Siebuhr AS, Uitterlinden AG, Oei EH, Hofman A, Karsdal MA, Bierma-Zeinstra SM, Bay-Jensen AC, van Meurs JB
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 co...
February 10, 2016
Journal:
Biomarkers
Author:
Bay-Jensen AC, Karsdal MA, Ladel C, Christiansen TG, Siebuhr AS, Kjelgaard-Petersen CF
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 and n...
December 21, 2015
Journal:
Biomarkers
Author:
Kluzek S, Bay-Jensen AC, Judge A, Karsdal MA, Shorthose M, Spector T, Hart D, Newton JL, Arden NK
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. M...
December 2, 2015
Journal:
Clin J Pain
Author:
Petersen KK, Siebuhr AS, Graven-Nielsen T, Simonsen O, Boesen MP, Gudbergsen H, Karsdal MA, Bay-Jensen AC, Arendt-Nielsen L
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...
October 20, 2015
Journal:
Scand J Rheumatol
Author:
Siebuhr AS, Bay-Jensen AC, Jordan JM, Kjelgaard-Petersen CF, Christiansen C, Abramson SB, Attur M, Berenbaum F, Kraus VB, Karsdal MA
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...
May 10, 2015
Journal:
Biomarkers.
Author:
Madsen SH, Sumer EU, Bay-Jensen AC, Sondergaard BC, Qvist P, Karsdal MA
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 Arth...
April 1, 2015
Journal:
Osteoarthritis Cartilage
Author:
Karsdal MA, Bihlet AR, Byrjalsen I, Alexandersen P, Ladel C, Michaels M, Andersen JR, Riis BJ, Kraus VB, Bay-Jensen AC, Christiansen C
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