期刊
STEM CELL RESEARCH & THERAPY
卷 13, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13287-022-03092-8
关键词
Irisin; Human mesenchymal stem cells; Chondrogenic differentiation; Rap1; PI3K; AKT signaling pathway; miR-125b-5p
资金
- National Natural Science Foundation of China [82072473]
- Guangdong Basic and Applied Basic Research Foundation [2021A1515012619]
- Fundamental Research Funds of the Central Universities [20ykpy94]
- Science and Technology Program of Guangzhou, China [202102010159]
- Postdoctoral Science Foundation of China [2020TQ0385]
- Sun Yat-sen Scholarship for Young Scientist
This study demonstrates that irisin can significantly enhance chondrogenic differentiation of hMSCs via the Rap1/PI3K/AKT pathway, showing prospects for cartilage regeneration.
Background Human mesenchymal stem cells (hMSCs) have been proven to have inherent chondrogenic differentiation potential, which appears to be used in cartilage regeneration. Increasing evidence suggests that irisin enhances osteoblast differentiation of MSCs, but little is known about its potential on chondrogenic differentiation. Methods In the study, we investigated the effects of irisin on chondrogenic differentiation of hMSCs using a high-density pellet culture system. The cartilage pellets were evaluated by morphology, and the metabolism of cartilage matrix was detected by qPCR, western blot and immunohistochemistry. Next, RNA-seq was performed to explore the underlying mechanism. Furthermore, using the transduction of plasmid, miRNAs mimics and inhibitor, the activation of Rap1/PI3K/AKT axis, the expression level of SIPA1L2, and the functional verification of miR-125b-5p were detected on day 7 of chondrogenic differentiation of hMSCs. Results Compared with the controls, we found that irisin treatment could significantly enhance the chondrogenic differentiation of hMSCs, enlarge the induced-cartilage tissue and up-regulate the expression levels of cartilage markers. RNA-seq indicated that irisin activated the Rap1 and PI3K/AKT signaling pathway, and the lower expression level of SIPA1L2 and the higher expression level of miR-125b-5p were found in irisin-treated group. Further, we found that irisin treatment could up-regulate the expression level of miR-125b-5p, targeting SIPA1L2 and consequently activating the Rap1/PI3K/AKT axis on the process of chondrogenic differentiation of hMSCs. Conclusions Collectively, our study reveals that irisin can enhance chondrogenic differentiation of hMSCs via the Rap1/PI3K/AKT pathway, suggesting that irisin possesses prospects in cartilage regeneration.
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