High Expression of the Tyrosine Kinase Fyn Causes Accelerated Differentiation of Growth Plate Chondrocytes in Young Rats with Chronic Renal Failure

Background: To observe the effect of high expression of the tyrosine kinase Fyn on chondrocyte differentiation in the tibial growth plate of young rats with chronic renal failure (CRF) and to explore the related molecular mechanism. Methods: The level of Fyn, the levels of the key Wnt/β-catenin pathway protein β-catenin and its phosphorylated form, p-β-catenin (Tyr142), and the level of the chondrocyte differentiation marker collagenX were observed in the CRF group in vivo and in vitro. The direct effect of Fyn and p-β-catenin in the cytoplasm of chondrocytes of rats with CRF was observed by using coimmunoprecipitation (co-IP). The levels of p-β-catenin (Tyr142), β-catenin and collagenX were observed after altering the Fyn levels in the chondrocytes of rats with CRF. Results: When CRF occurred in young rats, the level of Fyn in chondrocytes increased, the levels of p-β-catenin (Tyr142) and β-catenin in the Wnt/β-catenin pathway increased, and the level of the chondrocyte differentiation marker collagenX increased. The levels of p-β-catenin (Tyr142), β-catenin and collagenX were obviously increased when the Fyn level was increased in the chondrocytes of rats with CRF. In contrast, the levels of p-β-catenin (Tyr142), β-catenin and collagenX significantly decreased when the Fyn level was decreased. The Fyn protein and the p-β-catenin (Tyr142) protein directly interacted in the cytoplasm of the chondrocytes from the CRF group. Conclusion: The level of the tyrosine kinase Fyn in the tibial growth plate chondrocytes of young rats with CRF significantly increased, and the levels of the wnt/β-catenin pathway-related protein β-catenin and its phosphorylated form, p-β-catenin (Tyr142), significantly increased. Fyn could promote β-catenin phosphorylation (Tyr142) and cause it to be released from the α-catenin and cadherin complex and enter the cytoplasm of chondrocytes. p-β-catenin (Tyr142) could be transformed into β-catenin by dynamic equilibrium in the cytoplasm of chondrocytes, or p-β-catenin (Tyr142) could enter the nucleus of chondrocytes from the cytoplasm, thus activating the wnt/β-catenin pathway and accelerating the differentiation of chondrocytes. Funding: This work was supported by grants from the China Postdoctoral Science Foundation (2020M680910), Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province (no.20210019),the Natural Science Foundation of Shanxi Province of China (no. 201701D121161) and the Key Research and Development Projects of Shanxi Province (no. 201803D31160). Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Ethics Committee of Shanxi Medical University [Approval number:SXMUE(2019004)] (Tai Yuan,China).