N-Acetyl-L-cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem/progenitor cells by enhancing the integrin α5/β1/PI3K/AKT signaling
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | BMC Molecular and Cell Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12860-022-00463-0 |
| _version_ | 1797958391568531456 |
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| author | Kang Lu Mei Zhou Liyuan Wang Yang Wang Hong Tang Gang He Huan Wang Chuyue Tang Jie He Wei Wang Kanglai Tang Yunjiao Wang Zhongliang Deng |
| author_facet | Kang Lu Mei Zhou Liyuan Wang Yang Wang Hong Tang Gang He Huan Wang Chuyue Tang Jie He Wei Wang Kanglai Tang Yunjiao Wang Zhongliang Deng |
| author_sort | Kang Lu |
| collection | DOAJ |
| description | Abstract 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 µM 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 α5β1 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. |
| first_indexed | 2024-04-11T00:19:21Z |
| format | Article |
| id | doaj.art-1899b8acd0d94e02902fdb0119d8f5f3 |
| institution | Directory Open Access Journal |
| issn | 2661-8850 |
| language | English |
| last_indexed | 2024-04-11T00:19:21Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Molecular and Cell Biology |
| spelling | doaj.art-1899b8acd0d94e02902fdb0119d8f5f32023-01-08T12:23:21ZengBMCBMC Molecular and Cell Biology2661-88502023-01-0124111310.1186/s12860-022-00463-0N-Acetyl-L-cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem/progenitor cells by enhancing the integrin α5/β1/PI3K/AKT signalingKang Lu0Mei Zhou1Liyuan Wang2Yang Wang3Hong Tang4Gang He5Huan Wang6Chuyue Tang7Jie He8Wei Wang9Kanglai Tang10Yunjiao Wang11Zhongliang Deng12Department of Orthopedics-Spine Surgery Center, the Second Affiliated Hospital, Chongqing Medical UniversityDepartment of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical UniversityDepartment of Orthopedics-Spine Surgery Center, the Second Affiliated Hospital, Chongqing Medical UniversityDepartment of Orthopedics-Spine Surgery Center, the Second Affiliated Hospital, Chongqing Medical UniversityDepartment of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical UniversityDepartment of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical UniversityDepartment of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical UniversityDepartment of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical UniversityDepartment of Orthopedics-Spine Surgery Center, the Second Affiliated Hospital, Chongqing Medical UniversityDepartment of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical UniversityDepartment of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical UniversityDepartment of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical UniversityDepartment of Orthopedics-Spine Surgery Center, the Second Affiliated Hospital, Chongqing Medical UniversityAbstract 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 µM 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 α5β1 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.https://doi.org/10.1186/s12860-022-00463-0NACTSPCsDifferentiationTendon injuryRats |
| spellingShingle | Kang Lu Mei Zhou Liyuan Wang Yang Wang Hong Tang Gang He Huan Wang Chuyue Tang Jie He Wei Wang Kanglai Tang Yunjiao Wang Zhongliang Deng N-Acetyl-L-cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem/progenitor cells by enhancing the integrin α5/β1/PI3K/AKT signaling BMC Molecular and Cell Biology NAC TSPCs Differentiation Tendon injury Rats |
| title | N-Acetyl-L-cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem/progenitor cells by enhancing the integrin α5/β1/PI3K/AKT signaling |
| title_full | N-Acetyl-L-cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem/progenitor cells by enhancing the integrin α5/β1/PI3K/AKT signaling |
| title_fullStr | N-Acetyl-L-cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem/progenitor cells by enhancing the integrin α5/β1/PI3K/AKT signaling |
| title_full_unstemmed | N-Acetyl-L-cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem/progenitor cells by enhancing the integrin α5/β1/PI3K/AKT signaling |
| title_short | N-Acetyl-L-cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem/progenitor cells by enhancing the integrin α5/β1/PI3K/AKT signaling |
| title_sort | n acetyl l cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem progenitor cells by enhancing the integrin α5 β1 pi3k akt signaling |
| topic | NAC TSPCs Differentiation Tendon injury Rats |
| url | https://doi.org/10.1186/s12860-022-00463-0 |
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