Molecular and Cellular Pathways Contributing to Joint Damage in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis is a chronic autoimmune syndrome associated with several genetic, epigenetic, and environmental factors affecting the articular joints contributing to cartilage and bone damage. Although etiology of this disease is not clear, several immune pathways, involving immune (T cells, B cells, dendritic cells, macrophages, and neutrophils) and nonimmune (fibroblasts and chondrocytes) cells, participate in the secretion of many proinflammatory cytokines, chemokines, proteases (MMPs, ADAMTS), and other matrix lysing enzymes that could disturb the immune balance leading to cartilage and bone damage. The presence of autoantibodies preceding the clinical onset of arthritis and the induction of bone erosion early in the disease course clearly suggest that initiation events damaging the cartilage and bone start very early during the autoimmune phase of the arthritis development. During this process, several signaling molecules (RANKL-RANK, NF-κB, MAPK, NFATc1, and Src kinase) are activated in the osteoclasts, cells responsible for bone resorption. Hence, comprehensive knowledge on pathogenesis is a prerequisite for prevention and development of targeted clinical treatment for RA patients that can restore the immune balance improving clinical therapy.

Osteoporosis in Rheumatoid Arthritis: Dangerous Liaisons

“…Indeed, osteoclasts, osteoblasts and osteocytes are the main cellular actors involved in bone remodeling. Different signaling pathways of these and other cells of the immune system regulate their function and bone remodeling (25)(26)(27)(28)(29) (Figure 2). Indeed, the bone and the immune system maintain a close relationship both anatomicalsince the bone houses the bone marrow-and functional through different molecular and cellular signaling pathways and a myriad of cytokines (25,26,28,29).…”

“…RA is the prototype of osteoimmunologic disease where bone loss is one of the most characteristic findings. In RA, there are three kind of bone loss: local, juxta-articular and systemic, causing periarticular osteopenia, bone erosions and generalized osteopenia and/or osteoporosis far from inflamed joints, respectively (25)(26)(27). The misbalance in bone remodeling that occurs in RA causes an increase in bone resorption that leads to a reduction of bone mass and a decrease in bone formation that inhibits bone repair.…”

Protective Effect of Epigallocatechin-3-Gallate (EGCG) in Diseases with Uncontrolled Immune Activation: Could Such a Scenario Be Helpful to Counteract COVID-19?

“…Rheumatoid arthritis (RA) is an autoimmune disease with persistent inflammation of synovial joints which can lead to articular bone and cartilage disruption [ 19 ].…”

Cynanchum paniculatum and Its Major Active Constituents for Inflammatory‐Related Diseases: A Review of Traditional Use, Multiple Pathway Modulations, and Clinical Applications

“…Upon activation of the MAP kinases, transcription factors are phosphorylated and activated leading to a series of biological responses. In chronic bowel diseases, stroke, Alzheimer's disease, arthritis, and other chronic inflammation related diseases, MAPK pathways are frequently activated and identified as the inhibitor for drug development [ 33 – 35 ]. Cynanchum paniculatum and its derivatives have shown anti-inflammatory activities through suppressing lipopolysaccharides- (LPS-) induced inflammatory cytokines in macrophage as well as blocking MAPK/ERK/p38 signaling pathway [ 27 , 36 ].…”