Osteoarthritis of the knee is a chronic, degenerative osteoarthropathy caused by local injury, inflammation or chronic strain on the knee joint, resulting in degeneration of the knee cartilage and impaired mobility. Its etiology is mainly caused by mechanical and biological factors, and the pathological process is complex, and many links have not been fully revealed. 1, joint stress balance imbalance When the joint is loaded, the cartilage is deformed and the arch fibrous structure is subjected to the pressure transmitted along the collagen fiber direction and dispersed to the subchondral bone, when unloaded, the pressure disappears and the fiber returns to its original shape, during which the chondrocytes are always protected within the fiber grid. However, when the load conduction is disturbed, the arch structure of the cartilage matrix will be destroyed and the chondrocytes will lose their protective role and be damaged . The current study concluded that, under the action of pathogenic factors, inflammatory cytokines mediated the elevated expression of various proteases in articular cartilage and synovium, causing degradation of the collagen fibrous network and proteoglycans of the articular cartilage matrix, which eventually leads to cartilage degeneration, and proteases play a key role in this pathological process. collagenase concentration in OA synovial fluid is more than 50% higher than in normal joint groups, and the enzyme inhibitor tissue The concentration of collagenase in the synovial fluid of OA joints was more than 50% higher than in the normal group, while the matrix metalloproteinase inhibitor was not significantly different from the normal control. The role of free radicals Haklar et al. had used 44 OA patients compared with normal controls and found that the level of reactive oxygen species was significantly higher in OA patients with cartilage damage.Delcarlo et al. It was demonstrated that NO-mediated chondrocyte death also requires the involvement of reactive oxygen species. Thus, not only the survival of chondrocytes but also their type of death depends on the balance between different free radicals. Available data suggest that apoptosis is likely to be an important link in the pathogenesis of OA, and the relationship between the two is worth exploring. 4, the relationship between osteoporosis (OP) and OA The clinical findings of Jordan et al. showed that the odds of femoral neck fracture were reduced in patients with OA of the hip at the same age. The analysis suggested that OA made TGF-β active, thus prolonging the osteoblast effect and preventing the occurrence of local OP. However, not all studies support a correlation between OA and high BMD levels. Especially when a narrow joint cavity is considered to be a major feature of OA, increased bone density can only be seen as a specific site of OA. In patients with knee OA an increase in lumbar spine BMD is generally reported, but not in hip BMD. Furthermore, the formation of osteophytes may be the result of abnormal healing of subchondral trabecular stress fractures at the joint margins. Lin Hua analyzed the dual-energy x-ray bone density of the lumbar spine in 200 patients diagnosed with knee osteoarthritis and found that they all had varying degrees of osteoporosis, speculating that there may be some intrinsic link between the two. Osteoporosis is likely to be one of the causes of osteoarthritis disease. 5, the relationship between the level of sex hormones and OA OA occurs in postmenopausal women, estrogen deficiency may be one of the main reasons for the development of OA. It has been confirmed that: many animals, including human articular chondrocytes and growth plate chondrocytes on the presence of estrogen receptors (α, β), which fully indicates that articular cartilage is the target tissue of estrogen. The articular cartilage of ovariectomized rats was thinned, the number of cell divisions was reduced, the rate of proteoglycan synthesis was decreased, and chondrocyte synthesis of type II collagen and matrix was reduced. Women who have taken estrogen in the past 10 years or are currently taking estrogen have a lower incidence of OA, and taking estrogen can slow down the onset of knee OA. 6, the role of cytokines and growth factors cytokines and growth factors are widely present in various tissues, they play an important regulatory role in the occurrence and development of a variety of diseases from the molecular level. Tumor necrosis factor (TNF-α) can promote the production of collagenase and prostaglandin (PG ) release protease activity and can induce peroxidation of osteoblasts, it is involved in promoting cartilage resorption together with IL-1. In an animal model of OA, immunohistochemical staining of OA cartilage showed positive reactions for TNF-α and receptors in the stroma and cells, and the intensity paralleled the extent and severity of OA. The first cartilage-stimulating growth factor extracted was insulin-like growth factor (IGF), which was divided into IGF-I and IGF-II types. It has been shown that IGF-I can stimulate articular cartilage matrix synthesis and inhibit chondrocyte-mediated matrix breakdown. Insulin-like growth factor binding protein 3, on the other hand, binds to IGF-I and competitively inhibits the binding of IGF-I to the receptor, thereby inhibiting the physiological activity of IGF. It has been found that IGF-I is elevated in osteoarthritic synovial fluid, but osteoarthritic cartilage is hyporesponsive to IGF-I by a mechanism related to insulin-like growth factor binding proteins. Elevated IGF-I in osteoarthritic synovial fluid, higher rise in insulin-like growth factor binding protein 3 levels, higher than normal insulin-like growth factor binding protein 3/IGF-I ratio, and normal IGF-I receptor expression resulted in a large amount of insulin-like growth factor binding protein 3 inhibiting IGF-I activity and participating in the formation of osteoarthritis. 7. the relationship between subchondral bone and OA Janet M et al. showed that morphological changes in subchondral bone preceded cartilage degeneration by radiography using a Dutch porcine knee model of osteoarthritis. jean-Pierre et al. concluded that subchondral bone loss and subchondral bone resorption were associated with the development of osteoarthritic cartilage lesions by histomorphological studies. cathering B. used a dog anterior cruciate ligament dissection OA model. The bone morphology study revealed that all ACL dissections showed signs of OA and accelerated articular cartilage degeneration and subchondral bone formation. Other factors such as immune response and endothelin (ET) also play an important role in the pathogenesis of OA. Thus, it can be seen that OA is caused by many factors, but the occurrence and development of OA lesions, as well as the mechanism of action is still a lot of unknown. Further research is needed to explore.