Effect and mechanism of metformin-modified bone marrow mesenchymal stem cell exosomes on regulating chondrocytes
- VernacularTitle:二甲双胍修饰骨髓间充质干细胞外泌体调节软骨细胞的作用及机制
- Author:
Xinli SIMA
1
;
Danping LIU
;
Hui QI
Author Information
- Publication Type:Journal Article
- Keywords: bone marrow mesenchymal stem cell; metformin; exosome; chondrocyte; osteoarthritis; oxidative stress; aging; engineered stem cell
- From: Chinese Journal of Tissue Engineering Research 2025;29(36):7728-7734
- CountryChina
- Language:Chinese
- Abstract: BACKGROUND:Osteoarthritis is a progressive joint condition identified by ongoing deterioration of the cartilage matrix,and there is currently no effective drug treatment plan.Metformin-modified exosomes isolated from bone marrow-derived mesenchymal stem cells can become a new method for treating osteoarthritis due to their avoidance of oral drug adverse reactions and immunogenicity.OBJECTIVE:To study the controlling impact of exosomes from metformin-altered bone marrow-derived mesenchymal stem cells on chondrocytes.METHODS:Rabbit bone marrow-derived mesenchymal stem cells and chondrocytes were cultured in vitro.Bone marrow-derived mesenchymal stem cells derived exosomes and metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes were collected using a high-speed centrifuge.Chondrocytes were cultured with exosome-containing culture medium for 24 hours and then treated with 100 μmol/L H2O2 for 24 hours.The capability changes of two extracellular vesicles on chondrocyte proliferation and migration were detected using CCK8 assay and scratch healing experiment,respectively.Western blot analysis and RT-qPCR were employed to examine the alterations in the expression of type Ⅱ collagen,P16 protein,and their mRNA in chondrocytes.Western blot analysis was utilized to assess the changes in the expression of MKK7/JNK pathway proteins.ELISA kits were utilized to measure the activity of cell superoxide dismutase and the levels of malondialdehyde in chondrocytes.RESULTS AND CONCLUSION:(1)In an oxidative stress environment,the proliferation and migration abilities of chondrocytes were weakened.The two types of exosomes could restore the proliferation and migration abilities of chondrocytes to a certain extent.Metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes had a significantly better improvement effect(P＜0.05).(2)Compared with normal bone marrow mesenchymal stem cell-derived exosomes,metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes could more effectively increase type Ⅱ collagen expression and superoxide dismutase activity(P＜0.05),and were also more effective in reducing P16 expression and malondialdehyde levels(P＜0.05).(3)The two types of exosomes could inhibit the expression of MKK7 and p-JNK proteins to a certain extent,and the inhibitory effect of metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes was more significant(P＜0.05).The results show that in an oxidative stress environment,metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes resist chondrocyte aging and promote chondrocyte proliferation by inhibiting the MKK7/JNK pathway.
