Exploration of Rongjin Niantong Formula Delaying Cartilage Degeneration in Mice with Knee Osteoarthritis Based on lncRNA MGC-Mirg and PERK Pathway
Objective:To Explore the mechanism of Rongjin Niantong formula in delaying cartilage degeneration in knee osteoar-thritis model mice based on the long non-coding RNA(lncRNA)MGC-Mirg and PRKR like endoplasmic reticulum kinase(PERK)pathway.Methods:Forty-eight 8-week-old mice were randomly divided into blank group(n=12)and modeling group(n=36)using a random number table method.The KOA model was established using the improved Hulth method in the modeling group.Successfully modeled rats were randomly divided into model group,Rongjin Niantong formula group and positive control group,with 12 rats in each group.The Rongjin Niantong formula group was given Rongjin Niantong formula solution by gavage at doses of 9.0 g/(kg·d);the positive control group was given taurine deoxycholic acid solution by gavage at doses of 500 mg/(kg·d);the blank and model groups were given saline by gavage at doses of 10 mL/(kg·d).All these intervention lasted 8 weeks.HE staining and safranin O-fast green staining were used to observe pathological changes in articular cartilage tissue;the protein expression of PERK,activating transcription factor 4(ATF4),binding immunoglobulin protein(BIP),ER degradation enhancing alpha-mannosidase like protein 1(EDEM1),growth arrest and DNA damage-inducible protein 153(GADD153),and Caspase-3 in cartilage tissue was detected by West-ern blot;the RNA expression level of lncRNA MGC-Mirg was detected by qPCR.Results:The pathology of the model group showed narrowing of the joint space,damage to the surface of cartilage membrane,deviation and thinning of the fiber direction in the cartilage layer,decreased number of chondrocytes,and collapse of the subchondral bone at the tibial plateau,with incomplete structures in each layer.Compared with the blank group,the protein expression level of PERK,ATF4,BIP,EDEM1,GADD153,Caspase-3,and the mRNA expression level of lncRNA MGC-Mirg in the knee joint cartilage tissue of the model group significantly increased(P<0.05).Compared with the model group,the structure of cartilage layer was basically intact in the Rongjin Niantong formula and positive con-trol groups;the protein expression level of PERK,ATF4,BIP,EDEM1,GADD153,Caspase-3,and the mRNA expression level of ln-cRNA MGC-Mirg in the knee joint cartilage tissue significantly decreased(P<0.05).Conclusion:Rongjin Niantong formula can effectively delay cartilage degeneration in KOA mice,and its mechanism may be related to the down-regulation the expression of lncRNA MGC-Mirg and PERK pathway-related protein,and inhibition of endoplasmic reticulum stress.
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