Onset and Progression of Human Osteoarthritis—Can Growth Factors, Inflammatory Cytokines, or Differential miRNA Expression Concomitantly Induce Proliferation, ECM Degradation, and Inflammation in Articular Cartilage?

Abstract

Osteoarthritis (OA) is a degenerative whole joint disease, for which no preventative or therapeutic biological interventions are available. This is likely due to the fact that OA pathogenesis includes several signaling pathways, whose interactions remain unclear, especially at disease onset. Early OA is characterized by three key events: a rarely considered early phase of proliferation of cartilage-resident cells, in contrast to well-established increased synthesis, and degradation of extracellular matrix components and inflammation, associated with OA progression. We focused on the question, which of these key events are regulated by growth factors, inflammatory cytokines, and/or miRNA abundance. Collectively, we elucidated a specific sequence of the OA key events that are described best as a very early phase of proliferation of human articular cartilage (AC) cells and concomitant anabolic/catabolic effects that are accompanied by incipient pro-inflammatory effects. Many of the reviewed factors appeared able to induce one or two key events. Only one factor, fibroblast growth factor 2 (FGF2), is capable of concomitantly inducing all key events. Moreover, AC cell proliferation cannot be induced and, in fact, is suppressed by inflammatory signaling, suggesting that inflammatory signaling cannot be the sole inductor of all early OA key events, especially at disease onset.

The Protective Effect of Dietary Administration of Puerarin on Canine Osteoarthritis Model With Anterior Cruciate Ligament Transected

“…Interleukin-1 β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) play a signi cant role in regulating the metabolism of chondrocytes and synovial cells. Articular cartilage is mainly composed of extracellular matrix and chondrocytes [19]. A large amount of proteoglycan and collagen form the network scaffold outside the cartilage cells, which play a role in supporting and shaping the cartilage cells.…”

Bioresponsive microspheres for on‐demand delivery of anti‐inflammatory cytokines for articular cartilage repair

“…OA is a degenerative joint disease that affects one or more diarthrodial joints and is commonly associated with inflammation and tissue breakdown. Although the etiology of OA is still elusive (Boehme & Rolauffs, 2018), chondrocytemediated inflammatory events driven by the stimulation of innate immune receptors by damage-associated molecules are thought to be the primary cause. OA starts with the "wear and tear" of the cartilage caused primarily due to trauma, obesity, and aging.…”

Proof-of-concept for the detection of early osteoarthritis pathology by endomicroscopy

“…Osteoarthritis (OA), the most common joint disorder, is a degenerative disease of the whole joint, for which no preventive or therapeutic biological interventions are available (6,7). OA is characterized by AC degradation and subchondral bone sclerosis, followed by loss of AC and complete destruction of the joint.…”

“…OA is characterized by AC degradation and subchondral bone sclerosis, followed by loss of AC and complete destruction of the joint. Research aiming at establishing a unified theory of the initial OA dysfunction has not been successful so far (6,8). The clinical diagnosis of OA relies on clinical symptoms and on imaging using x-ray and magnetic resonance imaging (MRI).…”