N-Acetyl-L-cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem/progenitor cells by enhancing the integrin alpha 5/beta 1/PI3K/AKT signaling

作者全名："Lu, Kang; Zhou, Mei; Wang, Liyuan; Wang, Yang; Tang, Hong; He, Gang; Wang, Huan; Tang, Chuyue; He, Jie; Wang, Wei; Tang, Kanglai; Wang, Yunjiao; Deng, Zhongliang"

作者地址："[Lu, Kang; Wang, Liyuan; Wang, Yang; He, Jie; Deng, Zhongliang] Chongqing Med Univ, Affiliated Hosp 2, Spine Surg Ctr, Dept Orthoped, 74 Linjiang Rd, Chongqing, Peoples R China; [Zhou, Mei; Tang, Hong; He, Gang; Wang, Huan; Tang, Chuyue; Wang, Wei; Tang, Kanglai; Wang, Yunjiao] Army Med Univ, Mil Med Univ 3, Southwest Hosp, Sports Med Ctr,State Key Lab Trauma Burn & Combin, 29 Yanzheng St, Chongqing, Peoples R China"

通信作者："Deng, ZL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Spine Surg Ctr, Dept Orthoped, 74 Linjiang Rd, Chongqing, Peoples R China.; Tang, KL; Wang, YJ (通讯作者)，Army Med Univ, Mil Med Univ 3, Southwest Hosp, Sports Med Ctr,State Key Lab Trauma Burn & Combin, 29 Yanzheng St, Chongqing, Peoples R China."

来源：BMC MOLECULAR AND CELL BIOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000909657900001

JCR分区：Q4

影响因子：2.4

年份：2023

卷号：24

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：NAC; TSPCs; Differentiation; Tendon injury; Rats

摘要："Background Tendon injury is associated with oxidative stress, leading to reactive oxygen species (ROS) production and inflammation. N-acetyl-L-cysteine (NAC) is a potent antioxidant. However, how NAC affects the biological functions of tendon stem/progenitor cells (TSPCs) and tendon repair has not been clarified.Method The impacts of NAC on the viability, ROS production, and differentiation of TSPCs were determined with the cell counting kit-8, fluorescence staining, Western blotting, and immunofluorescence. The effect of NAC on gene transcription in TSPCs was analyzed by transcriptomes and bioinformatics and validated by Western blotting. The potential therapeutic effect of NAC on tendon repair was tested in a rat model of Achilles tendon injury.Results Compared with the untreated control, treatment with 500 mu M NAC greatly promoted the proliferation of TSPCs and significantly mitigated hydrogen peroxide-induced ROS production and cytotoxicity in vitro. NAC treatment significantly increased the relative protein expression of collagen type 1 alpha 1 (COL1A1), tenascin C (TNC), scleraxis (SCX), and tenomodulin (TNMD) in TPSCs. Bioinformatics analyses revealed that NAC modulated transcriptomes, particularly in the integrin-related phosphoinositide 3-kinase (PI3K)/AKT signaling, and Western blotting revealed that NAC enhanced integrin alpha 5 beta 1 expression and PI3K/AKT activation in TSPCs. Finally, NAC treatment mitigated the tendon injury, but enhanced the protein expression of SCX, TNC, TNMD, and COLIA1 in the injured tissue regions of the rats.Conclusion NAC treatment promoted the survival and differentiation of TSPCs to facilitate tendon repair after tendon injury in rats. Thus, NAC may be valuable for the treatment of tendon injury."

基金机构：Chongqing postdoctoral science foundation; Chongqing talents funding [CSTB2022NSCQ-BHX0614]; National Science Foundation for Young Scientists of China [CQYC2021059825]; Chongqing Science & Technology Commission [82002306]; Sports Injury Repair and Reconstruction Research Innovation Group [cstc2021jcyj-msxmX0137]; [cstc2020jcyj-cxttX0004]

基金资助正文："The research was supported by grants from the Chongqing postdoctoral science foundation (CSTB2022NSCQ-BHX0614), the Chongqing talents funding (No. CQYC2021059825), the National Science Foundation for Young Scientists of China (No. 82002306), the Chongqing Science & Technology Commission (No. cstc2021jcyj-msxmX0137) and Sports Injury Repair and Reconstruction Research Innovation Group (No. cstc2020jcyj-cxttX0004)."