Cell-cell Discussion

Cartilage degradation and osteoarthritis: can lack of mechanical stimulation and subchondral bone insufficiency upregulate catabolic genes?

Problem or question being addressed

The bald truth is: articular cartilage cover may be reduced/lost when subchondral bone cannot bear it anymore. Several studies have shown that mechanical and biological insufficiency of the subchondral bone may precede joint cartilage degeneration. Of course, cartilage damage can be the primary event and cause secondary changes in the subchondral bone. Either way, increasing evidence points to a cross-talk between chondrocytes and subchondral bone cells leading to articular degeneration. The cascade of events that follows involves a reduction in the physiological load to which the subchondral region must be subjected, production of inflammatory cytokines, increased bone resorption, reactive increase in bone formation/subchondral sclerosis, neoangiogenesis, cartilage degradation and a cycle of self-destruction. The resulting osteoarthritis, affects millions of people around the world, causing chronic pain, joint deformity, functional limitation,…

Title

The role of extracellular vesicles in rheumatoid arthritis development and methotrexate treatment response

Background

Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily manifests in synovial joints but it may also lead to systemic alterations. Methotrexate (MTX) is often the initial drug prescribed to RA patients and 53-71% of patients have been reported to respond well to this treatment (1). Still, there is a large fraction of non-responding patients that must undergo consecutive trials to find a treatment that prevents joint degradation, maximize physical function and alleviate pain. This emphasizes the need for diagnostic and prognostic biomarkers. Extracellular vesicles (EVs) are important in cell-cell communication and have received an increased focus for their role in RA pathogenesis, as well as in studies of treatment response (2, 3). EVs are membrane-derived nanoparticles that carry proteins, lipids, DNA, and RNA, and are released by cells into biological fluids and tissues(4).

Problem or question being addressed: Investigating the role of endothelial-epithelial crosstalk in the regulation of ATII cells differentiation and its possible therapeutic implications in idiopathic pulmonary fibrosis. Rationale for your approach: Pulmonary fibrosis (PF) is a progressive disease in which scarring of lung tissue leads to death from respiratory failure (1). Currently available drugs, pirfenidone and nintedanib, have only a modest effect on survival (2). The lack of effective therapies is likely due to a poor understanding of the pathogenetic mechanisms driving disease onset and progression, especially in its idiopathic form (Idiopathic Pulmonary Fibrosis, IPF) (3). While lung fibroblasts are clearly the ultimate effectors of fibrotic tissue deposition(4), emerging evidence indicates that IPF should be considered an epithelium-driven disease (5). The alveolar epithelium is composed of fully differentiated alveolar type I (ATI) cells, which perform gas exchange, and alveolar type II (ATII) cells, which produce surfactant proteins and act as progenitor…

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