伤科益肾壮骨丸调控Hippo-YAP/TAZ通路对膝骨关节炎大鼠软骨的影响OA

Objective To investigate the effects of Shangke Yishen Zhuanggu Pills on cartilage morphology in rats with knee osteoarthritis(KOA)by regulating the Hippo-YAP/TAZ pathway.Methods SD successfully modeled SD rats were divided into sham-operated group,model group,model+Shangke Yishen Zhuanggu Pills(0.5 g·kg-1)group,model+Shangke Yishen Zhuanggu Pills+si-NC group,and model+Shangke Yishen Zhuanggu Pills+si-LATS group,with 8 rats in each group.Morphological observation of rat knee articular cartilage was performed;Safranin O-Fast Green staining was used to observe the histomorphology of knee articular cartilage;TUNEL assay was conducted to detect chondrocyte apoptosis;immunohistochemical staining was performed to detect p-YAP1 expression;Western Blot was used to detect the expression of extracellular matrix and Hippo-YAP/TAZ pathway-related proteins.Results Compared with the sham-operated group,the knee articular cartilage in the model group appeared light yellow with a rough articular surface,ulcerated spots,and osteophytes;cartilage tissue showed pale Safranin O staining;the TUNEL-positive rate and MMP13 expression were significantly increased(P<0.05);while the expressions of Aggrecan(ACAN),Collagen type Ⅱ α1 chain(COL2A1),p-Large tumor suppressor kinase 1/2(p-LATS1/2),p-YAP1,and TAZ were significantly decreased(P<0.05).Compared with the model group,the knee articular cartilage in the model+Shangke Yishen Zhuanggu Pills group and the model+Shangke Yishen Zhuanggu Pills+si-NC group appeared milky white with a smooth articular surface,no cracks,and no osteophytes;cartilage tissue showed red staining;the TUNEL-positive rate and MMP13 expression were significantly decreased(P<0.05);while the expressions of ACAN,COL2A1,p-LATS1/2,p-YAP1,and TAZ were significantly increased(P<0.05);moreover,there was no statistically significant difference between the model+Shangke Yishen Zhuanggu Pills group and the model+Shangke Yishen Zhuanggu Pills+si-NC group(P>0.05).Compared with the model+Shangke Yishen Zhuanggu Pills+si-NC group,the knee articular cartilage in the model+Shangke Yishen Zhuanggu Pills+si-LATS group appeared light yellow with a rough,ulcerated articular surface;Safranin O staining was pale;the TUNEL-positive rate and MMP13 expression were significantly increased(P<0.05);while the expressions of ACAN,COL2A1,p-LATS1/2,p-YAP1,and TAZ were significantly decreased(P<0.05).Conclusion Shangke Yishen Zhuanggu Pills may alleviate knee articular cartilage degeneration and injury in rats with knee osteoarthritis by regulating the expression of key proteins in the Hippo-YAP/TAZ pathway,thereby maintaining normal cartilage morphology and extracellular matrix homeostasis.