Osteoarthritis, rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, all have one clear common denominator; an altered turnover of bone. However, this may be more complex than a simple change in bone matrix and mineral turnover. While these diseases share a common tissue axis, thei...
December 21, 2020
Journal:
BMC Musculoskelet Disord.
Author:
Thudium CS, Nielsen SH, Sardar S, Mobasheri A, van Spil WE, Lories R, Henriksen K, Bay-Jensen AC, Karsdal MA.
Background: Osteoarthritis (OA) is a progressive, chronic disease characterized by articular cartilage destruction. The pro-inflammatory cytokine IL-17 levels have been reported elevated in serum and synovial fluid of OA patients and correlated with increased cartilage defects and bone remodeling. T...
May 12, 2020
Journal:
BMC Rheumatol
Author:
Sinkeviciute D, Aspberg A, He Y, Bay-Jensen AC, Önnerfjord P
The ultimate hope of researchers and patients is a pathway to development of treatments for osteoarthritis to modify the disease process in addition to the symptoms. However, development of disease modifying drugs requires objective endpoints such as measures of joint structure, joint tissue homeost...
Sprifermin, recombinant human fibroblast growth factor 18 (rhFGF18), induces cartilage regeneration in knees of patients with osteoarthritis (OA). We hypothesized that a temporal multiphasic process of extracellular matrix (ECM) degradation and formation underlie this effect. We aimed to characteriz...
April 7, 2020
Journal:
Sci Rep
Author:
Reker D, Siebuhr AS, Thudium CS, Gantzel T, Ladel C, Michaelis M, Aspberg A, Berchtold MW, Karsdal MA, Gigout A, Bay-Jensen AC
Objectives: Clinical trials of new disease-modifying treatments for osteoarthritis should demonstrate a positive effect on a functional outcome or reduction in joint failure in order to be considered successful. Total joint replacement (TJR) surgery may be considered as joint failure, but great vari...
March 15, 2020
Journal:
Semin Arthritis Rheum
Author:
Bihlet A, Bjerre-Bastos JJ, Andersen JR, Byrjalsen I, Karsdal MA, Bay-Jensen AC
Objective: Links between pain and joint degradation are poorly understood. We investigated the role of activation of Toll-like receptors (TLR) by cartilage metabolites in initiating and maintaining the inflammatory loop in OA causing joint destruction. Methods: Synovial membrane explants (SMEs) wer...
November 14, 2019
Journal:
Osteoarthritis Cartilage
Author:
Sharma N, drobinski P, Kayed A, Chen Z, Kjelgaard-Petersen CF, Gantzel T, Karsdal MA, Michaels M, Ladel C, Bay-Jensen AC, Lindemann S, Thudium CS
Ex vivo culture systems cover a broad range of experiments dedicated to studying tissue and cellular function in a native setting. Cartilage is a unique tissue important for proper function of the synovial joint and is constituted by a dense extracellular matrix (ECM), rich in proteoglycan and type ...
Importance: Sprifermin is under investigation as a disease-modifying osteoarthritis drug. Objective: To evaluate the effects of sprifermin on changes in total femorotibial joint cartilage thickness in the more symptomatic knee of patients with osteoarthritis. Design, setting, and participants: FOR...
October 8, 2019
Journal:
JAMA.
Author:
Hochberg MC, Guermazi A, Guehring H, Aydemir A, Wax S, Fleuranceau-Morel P", Reinstrup Bihlet A, Byrjalsen I, Ragnar Andersen J, Eckstein F
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...
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
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
There is an increasing demand for accurate endotyping of patients according to their pathogenesis to allow more targeted treatment. We explore a combination of blood-based joint tissue metabolites (neoepitopes) to enable patient clustering through distinct disease profiles. We analysed data from two...
BACKGROUND: Osteoarthritis (OA) leads to joint failure and total joint replacement (TJR, either hip (H) or knee (K)). Worsening of pain and joint space narrowing are believed to be surrogates for joint failure; however, we hypothesize that TJR, as a reflection of joint failure, can be used as an end...
June 26, 2019
Journal:
BMC Musculoskelet Disord
Author:
Bager CL, Karsdal MA, Bihlet A, Thudium CS, Byrjalsen I, Bay-Jensen AC
OBJECTIVES: Pain and disability are the main clinical manifestations of osteoarthritis, for which only symptomatic therapies are available. Hence, there is a need for therapies that can simultaneously alter disease progression and provide pain relief. KBP is a dual amylin- and calcitonin-receptor ag...
June 5, 2019
Journal:
Osteoarthritis Cartilage
Author:
Katri A, Dabrowska A, Lövfall H, Karsdal MA, Andreassen KV, Thudium CS, Henriksen K
PURPOSE OF REVIEW: This review focuses on the molecular taxonomy of osteoarthritis from the perspective of molecular biomarkers. We discuss how wet biochemical markers may be used to understand disease pathogenesis and progression and define molecular endotypes of osteoarthritis and how these corres...
January 31, 2019
Journal:
Curr Opin Rheumatol
Author:
mobasheri A, Van Spil WE, Budd E, Uzieliene I, Bernotiene E, Bay-Jensen AC, Larkin J, Levesque MC, Gualillo O, Henrotin Y
OBJECTIVE: Phenotypic changes of chondrocytes toward hypertrophy might be fundamental in the pathogenesis of OA, of which type X collagen (Col10) is a well-known marker. The purpose was to develop a specific immunoassay for blood quantification of a newly identified neo-epitope of type X collagen to...
January 14, 2019
Journal:
Osteoarthritis Cartilage
Author:
He Y, Manon-Jensen T, Arendt-Nielsen L, Petersen KK, Christiansen T, Samuels J, Abramson S, Karsdal MA, Attur M, Bay-Jensen AC
There is a need for efficacious and safe pain treatments for OA (osteoarthritis). The nerve growth factor (NGF) antibody tanezumab is associated with high efficacy, but when combined with chronic NSAID treatment shows an increased risk of rapidly progressive osteoarthritis (RPOA) in a small group of...
December 18, 2018
Journal:
Osteoarthritis Cartilage
Author:
Karsdal MA, Verburg KM, West CR, Bay-Jensen AC
In 1992, the Food and Drug Administration (FDA) instituted the accelerated approval regulations that allow drugs or biologics for serious conditions that fill an unmet medical need to be approved on the basis of a surrogate endpoint or an intermediate clinical endpoint. The current definition of a s...
November 19, 2018
Journal:
Osteoarthritis Cartilage.
Author:
Kraus VB, Simon LS, Katz JN, Neogi T, Hunter D, Guermazi A, Karsdal MA
N-terminal propeptide of type II collagen (PIINP) is a biomarker reflecting cartilage formation. PIINP exists in two main splice variants termed as type IIA and type IIB collagen NH₂-propeptide (PIIANP, PIIBNP). PIIANP has been widely recognized as a cartilage formation biomarker. However, the utili...
November 6, 2018
Journal:
Int J Mol Sci
Author:
Luo Y, He Y, Gudmann NS, Henriksen K, Simonsen O, Ladel C, Michaels M, Mobasheri A, Karsdal MA, Bay-Jensen AC
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...
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