Patrik Önnerfjord

Lund University | LU · Department of Clinical Sciences, Lund

The molecular mechanisms that drive the onset and development of osteoarthritis (OA) remain largely unknown. In this exploratory study, we used a proteomic platform (SOMAscan assay) to measure the relative abundance of more than 6000 proteins in synovial fluid (SF) from knees of human donors with healthy or mildly degenerated tissues, and knees wit...

Objective To gain new insight into the molecular changes of the meniscus by comparing the proteome profiles of healthy controls with mild degeneration and end-stage osteoarthritis (OA). Method We obtained tissue plugs from lateral and medial menisci of 37 individuals (central part of the posterior horn) classified as healthy (n = 12), mild signs o...

Synovial fluid (SF) may contain cleavage products of proteolytic activities. Our aim was to characterize the degradome through analysis of proteolytic activity and differential abundance of these components in a peptidomic analysis of SF in knee osteoarthritis (OA) patients versus controls (n = 23). SF samples from end-stage knee osteoarthritis pat...

Degenerative meniscus lesions have been associated with both osteoarthritis etiology and its progression. We therefore sought to establish a human meniscus ex vivo model to study the meniscal response to cytokine treatment using a proteomics approach. Lateral menisci were obtained from five knee-healthy donors. The meniscal body was cut into vertic...

This review summarizes and exemplifies the current understanding of osteoarthritis in vitro models and describes their relevance for new insights in the future of osteoarthritis research. Our friend and highly appreciated colleague, Prof. Alan Grodzinsky has contributed greatly to the understanding of joint tissue biology and cartilage biomechanics...

Objective Synovial fluid contains proteins that may have been released from surrounding tissues, our aim was to gain new insights into the proteomic profiles of human synovial fluid in knees with and without osteoarthritis (OA). Methods We used synovial fluid from 11 patients with end-stage medial compartment knee OA, aspirated during total knee r...

Introduction During airway infection, upregulation of proinflammatory cytokines and subsequent immune cell recruitment is essential to mitigate bacterial infection. Conversely, during prolonged and non-resolving airway inflammation, neutrophils contribute to tissue damage and remodeling. This occurs during diseases including cystic fibrosis (CF) an...

Objective Meniscal calcifications are associated with the pathogenesis of knee osteoarthritis (OA). We propose a micro-computed tomography (μCT) based 3D analysis of meniscal calcifications ex vivo, including a new grading system. Method Human medial and lateral menisci were obtained from 10 patients having total knee replacement for medial compar...

Background Post-traumatic osteoarthritis (PTOA) does not currently have clinical prognostic biomarkers or disease-modifying drugs, though promising candidates such as dexamethasone (Dex) exist. Many challenges in studying and treating this disease stem from tissue interactions that complicate understanding of drug effects. We present an ex vivo hum...

Osteoarthritis (OA) is the most common joint disease, where articular cartilage degradation is often accompanied with sclerosis of the subchondral bone. However, the association between OA and tissue mineralization at the nanostructural level is currently not understood. Especially, it is technically challenging to study calcified cartilage, where...

Background The characterization of differential molecular endotypes in osteoarthritis (OA) is essential for enabling patient stratification to enhance clinical trials, facilitate the development of targeted and individualized treatments. Objectives This study aimed to characterize the profile and dynamics over 24 months (24M) of proteins present i...

The cartilage aggrecan proteoglycan is crucial for both skeletal growth and articular cartilage function. A number of aggrecan (ACAN) gene variants have been linked to skeletal disorders, ranging from short stature to severe chondrodyplasias. Osteochondritis dissecans is a disorder where articular cartilage and subchondral bone fragments come loose...

Background and aims: Endoscopy and the use of fecal calprotectin (fecal CP) are among the least favored methods for assessing disease activity by inflammatory bowel disease (IBD) patients; the handling/processing of fecal samples is also impractical. Therefore, we sought to develop a novel neo-epitope serum calprotectin ELISA, CPa9-HNE, with the a...

The underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear) and from deceased controls without knee OA. Synovial...

Design criteria for tissue-engineered materials in regenerative medicine include robust biological effectiveness, off-the-shelf availability, and scalable manufacturing under standardized conditions. For bone repair, existing strategies rely on primary autologous cells, associated with unpredictable performance, limited availability and complex log...

Articular cartilage is a dense extracellular matrix-rich tissue that degrades following chronic mechanical stress, resulting in osteoarthritis (OA). The tissue has low intrinsic repair especially in aged and osteoarthritic joints. Here we describe three pro-regenerative factors; fibroblast growth factor 2 (FGF2), connective tissue growth factor, bo...

Objectives There is an unmet medical need for biomarkers in OA which can be applied in clinical drug development trials. The present study describes the development of a specific and robust assay measuring type II collagen degradation (T2CM) and discusses its potential as a noninvasive translational biomarker. Methods A type II collagen specific n...

Osteoarthritis (OA) is the most common joint disease globally. In OA, articular cartilage degradation is often accompanied with sclerosis of the subchondral bone. However, the association between OA and tissue mineralization at the nanostructural level is currently not understood. Especially, it is technically challenging to identify calcified cart...

Objectives In this study, we apply a clustering method to proteomic data sets from bovine and human models of post-traumatic osteoarthritis (PTOA) to distinguish clusters of proteins based on their kinetics of release from cartilage and examined these groups for PTOA biomarker candidates. We then quantified the effects of dexamethasone (Dex) on the...

Objective Knee osteoarthritis (OA) is associated with meniscal degeneration that may involve disorganization of the meniscal collagen fiber network. Our aims were to quantitatively analyze the microstructural organization of human meniscus samples in 3D using micro-computed tomography (μCT), and to compare the local microstructural organization bet...

Articular cartilage is a dense extracellular matrix-rich tissue that degrades following chronic mechanical stress, resulting in osteoarthritis (OA). The tissue has low intrinsic repair especially in aged and osteoarthritic joints. Here we describe three pro-regenerative factors; fibroblast growth factor 2 (FGF2), connective tissue growth factor, bo...

Introduction Knee injury history and increased joint load, respectively, are major risk factors for the development of knee osteoarthritis (OA). Lower extremity muscle function, such as knee muscle strength, influence joint load and may be important for the onset of knee OA. However, the role of muscle function as a possible modifiable protective m...

A T-cell permissive tumor microenvironment, characterized by the presence of activated T cells and low fibrotic activity is crucial for response to immune checkpoint inhibitors (ICIs). Granzyme B has been shown to promote T-cell migration through the basement membrane by the degradation of type IV collagen. In this study, we evaluated the biomarker...

The underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins on a global level in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear) and from deceased controls without...

Objectives In this exploratory study, we used discovery proteomics to follow the release of proteins from bovine knee articular cartilage in response to mechanical injury and cytokine treatment. We also studied the effect of the glucocorticoid dexamethasone (Dex) on these responses. Design Bovine cartilage explants were treated with either cytokin...

Background: Non-invasive biomarkers for predicting response to immune checkpoint inhibitors (ICI) are urgently needed. Crucial for response to ICI's is a T-cell permissive tumor microenvironment (hot tumor), characterized by presence of activated T-cells and low fibrotic activity. Activated T-cells release the protease granzyme B (GzB), which can c...

Psoriatic arthritis (PsA) is a chronic musculoskeletal inflammatory disease found in up to 30% of psoriasis patients. Prolargin—an extracellular matrix (ECM) protein present in cartilage and tendon—has been previously shown elevated in serum of patients with psoriasis. ECM protein fragments can reflect tissue turnover and pathological changes; thus...

Background Altered extracellular matrix (ECM) remodelling is an important part of the pathology seen in joint degenerative diseases. Type II collagen is the most abundant ECM protein in the cartilage and provides the tissue with essential tensile strength in order to withstand high compressive loading. During cartilage erosion, type II collagen is...

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. The aim of this study was to characterize an IL-17...

Objective Recent research in knee osteoarthritis (OA) highlights the role of the meniscus in OA pathology. Our aim was to compare the proteomes of medial and lateral menisci from end-stage medial compartment knee OA patients, with reference menisci from knee-healthy deceased donors, using mass spectrometry. Design Tissue plugs of Ø3 mm were obtain...

Purpose: There is a need to investigate the age characteristics andnatural history of collagen turnover biomarkers to maximize theirpotential use in osteoarthritis (OA) (Tables 1 and 2). Collagen turnover isan essential part of growth and can vary as a function of age and disease. Several collagen turnover biomarkers, such as the formation of type...

The diagnosis of tendon injury relies on clinical signs and diagnostic imaging but imaging is subjective and does not always correlate with clinical signs. A molecular marker would potentially offer a sensitive and specific diagnostic tool that could also provide objective assessment of healing for the comparison of different treatments. Cartilage...

Glycosaminoglycan (GAG) chemical exchange saturation transfer (gagCEST) is a potential method for cartilage quality assessment. The aim of this study was to investigate how the gagCEST effect depends on the types and molecular organization of GAG typically found in articular cartilage. gagCEST was performed on different concentrations of GAG in var...

Recent research suggests an important role of the meniscus in development of knee osteoarthritis. We therefore aimed to analyze the proteome of the normal human meniscus body, and specifically to gain new knowledge on global protein expression in the different radial zones. Medial menisci were retrieved from the right knees of 10 human cadaveric do...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background An early detection of Osteoarthritis is urgently needed and still not possible until today. The aim of the study was to assess whether molecular biomarkers of cartilage turnover are associated with longitudinal change in knee cartilage thickness during a 2 year period in individuals with increased risk of developing knee osteoarthritis....

Background: Most in vitro studies of potential osteoarthritis (OA) therapies have used cartilage monocultures, even though synovium is a key player in mediating joint inflammation and, thereby, cartilage degeneration. In the case of interleukin-1 (IL-1) inhibition using its receptor antagonist (IL-1Ra), like chondrocytes, synoviocytes also express...

Osteopontin (OPN) plays a role in inflammation via recruitment of neutrophils and tissue remodeling. In this study, we investigated the distribution of OPN-expressing cells in the airway epithelium of normal lung tissue and that from patients with chronic obstructive pulmonary disease (COPD). OPN was detected on the epithelial cell surface of small...

A steady increase in the incidence of osteoarthritis and other rheumatic diseases has been observed in recent decades, including autoimmune conditions such as rheumatoid arthritis, spondyloarthropathies, systemic lupus erythematosus, systemic sclerosis and Sjögren's syndrome. Rheumatic and autoimmune diseases (RADs) are characterised by inflammatio...

Unlike highly regenerative animals, such as axolotls, humans are believed to be unable to counteract cumulative damage, such as repetitive joint use and injury that lead to the breakdown of cartilage and the development of osteoarthritis. Turnover of insoluble collagen has been suggested to be very limited in human adult cartilage. The goal of this...

Objective: To develop and perform ex vivo 3D imaging of meniscus posterior horn microstructure using micro-computed tomography (μCT), and to compare specimens from healthy references against end-stage osteoarthritis (OA) using conventional section-based histology and qualitative μCT. Design: We retrieved human medial and lateral menisci from 10...

Background Degenerative meniscal lesions are highly prevalent in the general population and are associated with increased risk of knee osteoarthritis (OA). Development of novel methods for visualization of the early degenerative changes in the meniscus could help us better understand meniscal degradation and the onset of OA. Objectives To develop...

Background There is a lack of valid and robust biomarkers in the field of OA diagnosis, prognosis, and treatment evaluation [1]. Synovial fluid is in direct contact with articular cartilage, ligament, meniscus and joint capsule it is therefore an excellent sample to explore the protein profile in which could provide pathogenesis information from se...

Objective: To investigate the relationship between meniscus magnetic resonance (MR) relaxation parameters and meniscus degradation through quantitative imaging of ex vivo posterior horns of menisci from subjects with and without knee osteoarthritis (OA). Design: We sampled medial and lateral menisci from ten medial compartment knee OA patients (...

Background Proteomics is an emerging field in the study of joint disease. Our two aims with this pilot analysis were to compare healthy human knee articular cartilage with meniscus, two tissues both known to become affected in the osteoarthritic disease process, and to compare two mass spectrometry (MS)-based methods: data-dependent acquisition (DD...

Abstract Objectives One mechanism by which cartilage responds to mechanical load is by releasing heparin-bound growth factors from the pericellular matrix (PCM). By proteomic analysis of the PCM, we identified connective tissue growth factor (CTGF) and here investigate its function and mechanism of action. Methods Recombinant CTGF (rCTGF) was us...