The Involvement of Neutrophils in the Pathophysiology and Treatment of Osteoarthritis

Abstract

Osteoarthritis (OA) is a chronic disability that significantly impairs quality of life. OA is one of the most prevalent joint pathologies in the world, characterized by joint pain and stiffness due to the degeneration of articular cartilage and the remodeling of subchondral bone. OA pathogenesis is unique in that it involves simultaneous reparative and degradative mechanisms. Low-grade inflammation as opposed to high-grade allows for this coexistence. Previously, macrophages and T cells have been identified as playing major roles in the inflammation and destruction of OA joints, but recent studies have demonstrated that neutrophils also contribute to the pathogenesis. Neutrophils are the first immune cells to enter the synovium after joint injury, and neutrophilic activity is indispensably a requisite for the progression of OA. Neutrophils act through multiple mechanisms including tissue degeneration via neutrophil elastase (NE), osteophyte development, and the release of inflammatory cytokines and chemokines. As the actions of neutrophils in OA are discovered, the potential for novel therapeutic targets as well as diagnostic methods are revealed. The use of chondrogenic progenitor cells (CPCs), microRNAs, and exosomes are among the newest therapeutic advances in OA treatment, and this review reveals how they can be used to mitigate destructive neutrophil activity.

Keywords: bone remodeling; cartilage degradation; exosomes; inflammation; microRNAs; neutrophil elastase; neutrophils; osteoarthritis; treatment.

Figure 1

The role of neutrophils in the early as well as late stages of osteoarthritis progression. Neutrophils are recruited at the synovial capsule and contribute to the secretion of many cytokines and chemokines within synovial fluid that promote inflammation and vascular infiltration and inhibit chondrogenic progenitor cell migration. The formation of neutrophil elastase (NE) enhances cartilage degradation, chondrocytes apoptosis, unbalanced subchondral bone remodeling, and osteophyte formation.