Research Progress on the Pathogenesis of Knee Osteoarthritis

Abstract

Knee osteoarthritis (KOA) is a chronic joint bone disease characterized by inflammatory destruction and hyperplasia of bone. Its main clinical symptoms are joint mobility difficulties and pain, severe cases can lead to limb paralysis, which poses major pressure to the quality of life and mental health of patients, but also brings serious economic burden to society. The occurrence and development of KOA is influenced by many factors, including systemic factors and local factors. The joint biomechanical changes caused by aging, trauma and obesity, abnormal bone metabolism caused by metabolic syndrome, the effects of cytokines and related enzymes, genetic and biochemical abnormalities caused by plasma adiponectin, etc. all directly or indirectly lead to the occurrence of KOA. However, there is little literature that systematically and comprehensively integrates macro- and microscopic KOA pathogenesis. Therefore, it is necessary to comprehensively and systematically summarize the pathogenesis of KOA in order to provide a better theoretical basis for clinical treatment.

Keywords: Bone Metabolism; Cytokines; Inflammation; Knee Osteoarthritis; Long Non-Coding RNA.

Fig. 1

Macroscopic factors affecting the occurrence and development of knee osteoarthritis.

Fig. 2

The role of proinflammatory factors in the pathogenesis of knee osteoarthritis schematic diagram. IL‐1β, TNF‐α, IL‐6, and other pro‐inflammatory factors bind to their corresponding receptors, activate NF‐kB and MAPK signaling pathways. By promoting the expression of ADAMT‐4, ADAMT‐5, MMP1, MMP3, MMP13, and other enzymes, it inhibits the synthesis of proteoglycans and collagen resulting in ECM degradation. In addition, the same signaling pathway can increase the expression of inflammatory mediators such as COX‐2, PGE‐2, NO, iNOS, and induce inflammatory factors such as IL‐6 and TNF‐α to aggravate the inflammatory response.

Fig. 3

Diagram of MAPK signaling pathway in knee osteoarthritis. The pathway diagram shows that factors such as IL‐1 and TNF‐a can be used as initiators of MAPK signaling pathway to mediate signal expression and participate in catabolic events such as cartilage degradation.

Fig. 4

Diagram of NF‐kB signaling pathway in knee osteoarthritis. The pathway diagram showed that IL‐1β, TNF‐α, and other factors could mediate signal expression as initiators of NF‐kB signaling pathway. TRAF6 and TAK1 are NF‐κB pathway hub factors, which ultimately lead to the expression of inflammatory factors such as IL‐8, IL‐1β, TNF‐α, A20, COX‐2, and MIP‐1β, leading to increased inflammation and ECM degradation.