Synovium and the Innate Inflammatory Network in Osteoarthritis Progression

Abstract

This review focuses on the recent advancements in the understanding of innate immunity in the pathogenesis of osteoarthritis, particularly with attention to the roles of damage-associated molecular patterns (DAMPs), pattern recognition receptors (PPRs), and complement in synovitis development and cartilage degradation. Endogenous molecular products derived from cellular stress and extracellular matrix disruption can function as DAMPs to induce inflammatory responses and pro-catabolic events in vitro and promote synovitis and cartilage degradation in vivo via PRRs. Some of the DAMPs and PRRs display various capacities in driving synovitis and/or cartilage degradation in different models of animal studies. New findings reveal that the inflammatory complement cascade plays a key in the pathogenesis of OA. Crosstalk between joint tissues such as synovium and cartilage communicated at the cellular level within the innate immune inflammatory network is implicated to play an important role in OA progression. Further studies on how the innate immune inflammatory network impacts the OA disease process at different stages of progression will lead to the development of new therapeutic strategies.

The Role of Innate Immunity in Osteoarthritis: When Our First Line of Defense Goes On the Offensive

“…Unlike the adaptive immune system, innate immunity relies on recognition of conserved motifs generated by pathogens or damage within the body (18). Damage to cellular and cartilage extracellular matrix products from trauma, microtrauma (from repetitive overuse) or normal aging generates damage-associated molecular patterns (DAMPs) that activate the innate immune system (15, 17). DAMPs can be fragments generated from proteins, proteoglycans or remnants of cellular breakdown, such a uric acid (16, 18, 19) (Table 1).…”

“…Activation of the innate immune system is intricately involved in initiation and perpetuation of this low-grade inflammation (15–17). Thus, OA pathology is the result of an imbalance between the anabolic and catabolic processes in the joint (11).…”

The Chondroprotective Role of Erythromycin in a Murine Joint Destruction Model

“…Although multiple studies showed that intra-articular injection of an IL-1β antagonist inhibited injury-induced OA, 8,9 no results of OA manipulation on IL-1β knockout animals have been demonstrated. It was reported that the knockout of TLR2 and TLR4 mildly protect against meniscectomy-induced OA, 53 suggesting that TLRs may be required for OA development. However, the lack of a complete rescue in OA progression in the TLR KO indicates that other factors are also involved in this process.…”

The importance of synovitis diagnosis in osteoarthritis patients in the evaluation of mean platelet volume

“…Recently, studies have demonstrated that synovial inflammation can be a significant factor in osteoarthritis pathogenesis [3]. The authors detected lower MPV values in osteoarthritis patients with synovitis.…”