Metabolic Dysregulation and Its Role in Postoperative Pain among Knee Osteoarthritis Patients.

Unlabelled: Knee osteoarthritis (KOA) is characterized by low-grade inflammation, loss of articular cartilage, subchondral bone remodeling, synovitis, osteophyte formation, and pain. Strong, continuous pain may indicate the need for joint replacement in patients with end-stage OA, although postoperative pain (POP) of at least a two-month duration persists in 10-40% of patients with OA.

Study Purpose: The inflammation observed in joint tissues is linked to pain caused by the production of proinflammatory cytokines.

Downregulation of Tumour Necrosis Factor α Gene Expression in Peripheral Blood Mononuclear Cells Cultured in the Presence of Tofacitinib Prior to Therapy Is Associated with Clinical Remission in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by pain, synovial hyperplasia, mononuclear cell infiltration, bone erosion and joint destruction. Efficacy of personalized therapy in RA is associated with correct choice of therapeutic agent and a possibility to predict its effect prior to treatment. Our objective was to examine the association of baseline expression of metalloproteinase (MMP)-9 and cathepsin K, which are involved in cartilage and bone degradation, as well as proinflammatory cytokines tumour necrosis factor (TNF)α and interleukin (IL)-1β in the peripheral blood mononuclear cells (PBMCs) obtained from patients with RA cultured with tofacitinib (TFCN) and remission achievement.

Putative Association between Low Baseline Gene Expression in the Peripheral Blood and Clinical Remission in Rheumatoid Arthritis Patients Treated with Tofacitinib.

We investigated the importance of the baseline expression of genes involved in energy generation, as prognostic biomarkers of the treatment response to tofacitinib in patients with rheumatoid arthritis (RA). Peripheral blood samples were obtained from 28 patients with RA who received 3 months of tofacitinib therapy from 26 healthy controls. Clinical response was evaluated based on the disease activity score, the erythrocyte sedimentation rate (DAS28-ESR), and the serum levels of ACPA, RF, CRP, and ESR.

Development of Postoperative Pain in Patients with End-Stage Knee Osteoarthritis Is Associated with Upregulation of Genes Related to Extracellular Matrix Degradation, Inflammation, and Apoptosis Measured in the Peripheral Blood before Knee Surgery.

Osteoarthritis (OA) pain implies an indication for joint replacement in patients with end-stage OA. However, chronic postoperative pain is observed in 10-40% of patients with OA. Here, we identified genes whose expression in the peripheral blood before surgery could denote the risk of postoperative pain development.

Insulin Resistance in Osteoarthritis: Similar Mechanisms to Type 2 Diabetes Mellitus.

Osteoarthritis (OA) and type 2 diabetes mellitus (T2D) are two of the most widespread chronic diseases. OA and T2D have common epidemiologic traits, are considered heterogenic multifactorial pathologies that develop through the interaction of genetic and environmental factors, and have common risk factors. In addition, both of these diseases often manifest in a single patient.

Increased baseline RUNX2, caspase 3 and p21 gene expressions in the peripheral blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis patients are associated with improved clinical response to methotrexate therapy.

Objective: To investigate the potential of the baseline gene expression in the whole blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis (RA) patients for predicting the response to methotrexate (MTX) treatment.

Methods: Twenty-six control subjects and 40 RA patients were examined. Clinical, immunological and radiographic parameters were assessed before and after 24 months of follow-up.

Deferoxamine Suppresses Collagen Cleavage and Protease, Cytokine, and COL10A1 Expression and Upregulates AMPK and Krebs Cycle Genes in Human Osteoarthritic Cartilage.

This study reports the effects of the iron chelator deferoxamine (DFO) on collagen cleavage, inflammation, and chondrocyte hypertrophy in relation to energy metabolism-related gene expression in osteoarthritic (OA) articular cartilage. Full-depth explants of human OA knee articular cartilage from arthroplasty were cultured with exogenous DFO (1-50 M). Type II collagen cleavage and phospho-adenosine monophosphate-activated protein kinase (pAMPK) concentrations were measured using ELISAs.

Rituximab Downregulates Gene Expression Associated with Cell Proliferation, Survival, and Proteolysis in the Peripheral Blood from Rheumatoid Arthritis Patients: A Link between High Baseline Autophagy-Related ULK1 Expression and Improved Pain Control.

Objective. To clarify molecular mechanisms for the response to rituximab in a longitudinal study. Methods.

Rheumatoid factor positivity is associated with increased joint destruction and upregulation of matrix metalloproteinase 9 and cathepsin k gene expression in the peripheral blood in rheumatoid arthritic patients treated with methotrexate.

We evaluated changes in gene expression of mTOR, p21, caspase-3, ULK1, TNF α , matrix metalloproteinase (MMP)-9, and cathepsin K in the whole blood of rheumatoid arthritic (RA) patients treated with methotrexate (MTX) in relation to their rheumatoid factor status, clinical, immunological, and radiological parameters, and therapeutic response after a 24-month follow-up. The study group consisted of 35 control subjects and 33 RA patients without previous history of MTX treatment. Gene expression was measured using real-time RT-PCR.

Differences in Mammalian target of rapamycin gene expression in the peripheral blood and articular cartilages of osteoarthritic patients and disease activity.

The gene expression of mTOR, autophagy-related ULK1, caspase 3, CDK-inhibitor p21, and TNF α was measured in the peripheral blood of osteoarthritic (OA) patients at different stages of the disease aiming to establish a gene expression profile that might indicate the activity of the disease and joint destruction. Whole blood of 65 OA outpatients, 27 end-stage OA patients, 27 healthy volunteers, and knee articular cartilages of 28 end-stage OA patients and 26 healthy subjects were examined. OA outpatients were subjected to clinical testing, ultrasonography, and radiographic and WOMAC scoring.

Developmental mechanisms in articular cartilage degradation in osteoarthritis.

Osteoarthritis is the most common arthritic condition, which involves progressive degeneration of articular cartilage. The most recent accomplishments have significantly advanced our understanding on the mechanisms of the disease development and progression. The most intriguing is the growing evidence indicating that extracellular matrix destruction in osteoarthritic articular cartilage resembles that in the hypertrophic zone of fetal growth plate during endochondral ossification.

Prostaglandin PGE2 at very low concentrations suppresses collagen cleavage in cultured human osteoarthritic articular cartilage: this involves a decrease in expression of proinflammatory genes, collagenases and COL10A1, a gene linked to chondrocyte hypertrophy.

Suppression of type II collagen (COL2A1) cleavage by transforming growth factor (TGF)-beta2 in cultured human osteoarthritic cartilage has been shown to be associated with decreased expression of collagenases, cytokines, genes associated with chondrocyte hypertrophy, and upregulation of prostaglandin (PG)E2 production. This results in a normalization of chondrocyte phenotypic expression. Here we tested the hypothesis that PGE2 is associated with the suppressive effects of TGF-beta2 in osteoarthritic (OA) cartilage and is itself capable of downregulating collagen cleavage and hypertrophy in human OA articular cartilage.

Chondrocyte hypertrophy can be induced by a cryptic sequence of type II collagen and is accompanied by the induction of MMP-13 and collagenase activity: implications for development and arthritis.

The objective of this study was to determine whether a peptide of type II collagen which can induce collagenase activity can also induce chondrocyte terminal differentiation (hypertrophy) in articulate cartilage. Full depth explants of normal adult bovine articular cartilage were cultured with or without a 24 mer synthetic peptide of type II collagen (residues 195-218) (CB12-II). Peptide CB12-II lacks any RGD sequence and is derived from the CB12 fragment of type II collagen.

Transforming growth factor-beta2 suppresses collagen cleavage in cultured human osteoarthritic cartilage, reduces expression of genes associated with chondrocyte hypertrophy and degradation, and increases prostaglandin E(2) production.

Articular cartilage degeneration in osteoarthritis (OA) involves type II collagen degradation and chondrocyte differentiation (hypertrophy). Because these changes resemble growth plate remodeling, we hypothesized that collagen degradation may be inhibitable by growth factors known to suppress growth plate hypertrophy, namely transforming growth factor (TGF)-beta2, fibroblast growth factor (FGF)-2, and insulin. Full-depth explants of human OA knee articular cartilage from arthroplasty were cultured with TGF-beta2, FGF-2, and insulin in combination (growth factors) or individually.

Increased type II collagen degradation and very early focal cartilage degeneration is associated with upregulation of chondrocyte differentiation related genes in early human articular cartilage lesions.

Objective: Articular cartilage degeneration in osteoarthritis (OA) involves excessive degradation of extracellular matrix (ECM) and chondrocyte differentiation (hypertrophy). We determined the interrelationship between the extent of collagen cleavage by collagenase, cartilage degeneration, and differentiation related gene expression in patella-femoral condylar cartilages of patients bearing very early focal OA-like articular cartilage lesions.

Methods: Articular cartilage specimens with very early focal lesions and adjacent normal cartilage from 3 donors were removed at autopsy as full-depth slices cut from the femoral condyle surface that articulates with patella.

Proteolysis involving matrix metalloproteinase 13 (collagenase-3) is required for chondrocyte differentiation that is associated with matrix mineralization.

Collagenases are involved in cartilage matrix resorption. Using bovine fetal chondrocytes isolated from physeal cartilages and separated into a distinct prehypertrophic subpopulation, we show that in serum-free culture they elaborate an extracellular matrix and differentiate into hypertrophic chondrocytes. This is characterized by expression of type X collagen and the transcription factor Cbfal and increased incorporation of 45Ca2+ in the extracellular matrix, which is associated with matrix calcification.