Molecular Mechanisms in Rheumatic Diseases: Rationale for Novel Drug Development - Introduction

U0126, an Inhibitor of MEK1/2, Increases Tumor Necrosis Factor-?-Induced Apoptosis, but not Interleukin-6 Induced Apoptosis in C-28/I2 Human Chondrocytes

“…Of note, the chronic inflammatory state of RA synovial joints resulting from autoimmune activation of T-cells, B-cells, macrophages, and other accessory cells (i.e., dendritic cells) of the innate and adaptive immune system [47-49], often results in both “apoptosis-resistance” in RA synovial tissue [50-52] and a reduction in chondrocyte vitality, the latter event generally attributed to the capacity of pro-inflammatory cytokines to induce apoptosis [24]. In addition, the profound loss of chondrocyte viability as OA progresses from an indolent state to an inflammatory disease believed to be generally accompanied by a process resulting from chondrocyte apoptosis is generally considered to be a hallmark of this disease process.…”

Chondrocyte Apoptosis in Rheumatoid Arthritis: Is Preventive Therapy Possible?

“…A subsequent analyses of RA cartilage reported several additional changes in RA cartilage which were consistent with an increased frequency of chondrocyte apoptosis. These included, evidence of natural killer activity in RA chondrocytes involving granzyme B activity [37], the latter enzyme having been implicated in poly-ADP-ribose polymerase degradation (PARP) [38] as well as high levels of TNF-α, IL-1β [39], and IL-8 [40]. Importantly.…”

Vaccine development for rheumatoid arthritis

“…Rheumatoid arthritis (RA) is a systemic, chronically progressive autoimmune disorder characterized by defective innate and adaptive immune responses [1][2][3][4][5]. Synovial joint inflammation, destruction of subchondral bone and articular cartilage, the latter occurring via degradation of cartilage extracellular matrix (ECM) as well as altered soft tissue structures, including those required to maintain the function of ligaments, capsule and tendons are also hallmarks of RA pathology [6][7][8].…”