动物造模,药效评价,骨关节 z-bio 2024-07-31 659

　　About 38% to 65% of OA patients have a genetic background in their etiology, suggesting that the cause of OA in these patients may be related to certain genetic mutations in themselves. Similar to humans, some animals also spontaneously produce OA as they age. In addition, genetically modified animals constructed using techniques such as genetic modification or gene knockout can also spontaneously form OA.

　　[Method of Modeling]

　　When male Hartly guinea pigs reach a weight of 700g at about 3 months old, osteoarthritis may appear on the medial tibial plateau of their knee joint. At 18 months old, severe pathological changes of osteoarthritis were observed on the medial tibial plateau of guinea pigs, and there was no meniscus coverage on the surface.

　　At approximately 12-20 weeks, knee osteoarthritis can be observed in STR/ort mice.

　　Biglycan and fibronectin are two small molecule proteoglycans co expressed in tissues such as tendons, cartilage, and bone in Bgn Fbn double gene knockout mice. Double gene knockout mice can produce ectopic ossification and OA lesions similar to those in STR/ort mice.

　　4. Cre-Gdf5/Bmpr1a floxP mice. The joint specific deficiency of bone morphogenetic protein (BMP) receptor protein expression in this gene modified mouse can lead to early multi joint OA lesions.

　　Other common genetically modified mouse OA models typically involve transgenic or gene knockout operations on genes encoding extracellular matrix proteins or related enzyme proteins in chondrocytes, in order to construct OA animal models. They include: type II collagen expression deficient mice, type IX collagen expression deficient mice, MMP-13 transgenic mice, Aggrencan gene knockout mice, etc.

　　[Model Features]

　　1. The spontaneous OA model of guinea pigs can observe OA changes in both the knee joint and other joints. OA manifests as cartilage degradation mainly through histological changes in the weight-bearing area, which is similar to the occurrence and development of human osteoarthritis. Abnormal distribution of glycosaminoglycans in cartilage. Research has found that the production of NO in knee chondrocytes of guinea pigs is positively correlated with age and the progression of OA, suggesting that it may be an important factor leading to mitochondrial dysfunction and calcification in OA chondrocytes.

　　The histological changes in STR/ort mice mainly manifest as severe degeneration of the medial articular cartilage similar to human OA, with calcification in the subchondral layer. This type of mouse also exhibits significantly increased release of local and systemic inflammatory factors, such as RAGE, AGE, IL-1, and IL-6.

　　The characteristics of Bgn Fbn double gene knockout mice and Cre-Gdf5/Bmpr1a floxP mice, two genetically modified animals, are characterized by non inflammatory fibrosis of the articular cartilage surface and gradual thinning of articular cartilage thickness in the early stages of OA.

　　[Model Evaluation and Application] Animal models of spontaneous OA formation have similar characteristics to human OA: the initial stage and progression of the disease are relatively mild, which is superior to other animal models. It is worth noting that due to the slow progression of the disease, early diagnosis of OA is difficult, and researchers need to pay attention to observing its pathological changes. In addition, the study also found that different treatment strategies may have different effects in spontaneous OA models and surgical induced models. Reagents that promote synthetic metabolism can effectively inhibit the spontaneous progression of OA in guinea pigs, but have no significant effect on alleviating the lesions induced by surgery in rabbit OA models.