Abstract
Objective To evaluate the effect of Kartogenin-pretreated exosomes derived from infrapatellar fat pad mesenchymal stem cells on chondrocyte in vitro and articular cartilage regeneration in vivo. Methods Infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) were isolated from rabbits to harvest exosomes. After identification of mesenchymal stem cells and exosomes, rabbit chondrocytes were divided into three groups for further treatment: the EXO group (chondrocytes treated with exosomes isolated from infrapatellar fat pad mesenchymal stem cells), KGN-EXO group (chondrocytes treated with exosomes isolated from infrapatellar fat pad mesenchymal stem cells pretreated with KGN), and control group. After processing and proliferation, phenotypic changes of chondrocytes were measured. In the in vivo study, 4 groups of rabbits with articular cartilage injury were treated with KGN-EXO, EXO, IPFP-MSCs, and control. Macroscopic evaluation and histological evaluation were made to figure out the different effects of the 4 groups on cartilage regeneration in vivo. Results The proliferation rate of chondrocytes in the EXO or KGN-EXO group was significantly higher than that in the control group (P < 0.05). The qRT-PCR results showed that the expression of Sox-9, Aggrecan, and Col II was the highest in the KGN-EXO group compared with the EXO group and the control group (P < 0.05). The results of Western blot were consistent with the results of qRT-PCR. In vivo, the cartilage defects in the KGN-EXO group showed better gross appearance and improved histological score than those in IPFP-MSC groups, EXO groups, and control groups (P < 0.05). At 12 weeks, the defect site in the KGN-EXO group was almost completely repaired with a flat and smooth surface, while a large amount of hyaline cartilage-like structures and no obvious cracks were observed. Conclusion Our study demonstrates that the exosomes isolated from infrapatellar fat pad mesenchymal stem cells pretreated with KGN have potent ability to induce chondrogenic differentiation of stem cells, effectively promoting the proliferation and the expression of chondrogenic proteins and genes of chondrocytes. The KGN-EXO can also promote the repair of articular cartilage defects more effectively, which can be used as a potential therapeutic method in the future.
Highlights
Osteoarthritis (OA) is one of the most common diseases encountered in the field of orthopedics
mesenchymal stem cells (MSCs) were cultured in three stages of differentiation: osteogenic, adipogenic, and chondrogenic stages, in order to identify their relative potential to differentiate in different directions
Since cells aged after multiple passages, we selected cells from passage 3 (P3) for experimentation
Summary
Osteoarthritis (OA) is one of the most common diseases encountered in the field of orthopedics. OA is a chronic degenerative joint disease that commonly causes pain and limited mobility. The treatment costs associated with OA are high [1]. There are many risk factors associated with OA, including genetic factors, female gender, a history of trauma, age, and obesity [4]. There are approximately 237 million people worldwide suffering from OA [5, 6]. Promoting articular cartilage repair or regeneration is the key to prevent OA progress. It is a worldwide challenge to promote articular cartilage regeneration or repair through current clinical methods, such as medications, physical therapy, arthroscopy, microfracture, or cartilage transplantation [7, 8]
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