Betaine enhances SCAPs chondrogenic differentiation and promotes cartilage repair in TMJOA through WDR81

Abstract Background The cartilage tissue regeneration mediated with mesenchymal stem cells (MSCs) is considered as a viable strategy for temporomandibular joint osteoarthritis (TMJOA). Betaine has been confirmed to modulate the multidirectional differentiation of MSCs, while its effect on chondrogen...

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Main Authors: Meiyue Wang, Zejie Wu, Xiaoyu Zheng, Yishu Huang, Yizhou Jin, Jiaxin Song, Wanzhen Lei, Hua Liu, Riyue Yu, Haoqing Yang, Runtao Gao
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Stem Cell Research & Therapy
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Online Access:https://doi.org/10.1186/s13287-025-04161-4
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author Meiyue Wang
Zejie Wu
Xiaoyu Zheng
Yishu Huang
Yizhou Jin
Jiaxin Song
Wanzhen Lei
Hua Liu
Riyue Yu
Haoqing Yang
Runtao Gao
author_facet Meiyue Wang
Zejie Wu
Xiaoyu Zheng
Yishu Huang
Yizhou Jin
Jiaxin Song
Wanzhen Lei
Hua Liu
Riyue Yu
Haoqing Yang
Runtao Gao
author_sort Meiyue Wang
collection DOAJ
description Abstract Background The cartilage tissue regeneration mediated with mesenchymal stem cells (MSCs) is considered as a viable strategy for temporomandibular joint osteoarthritis (TMJOA). Betaine has been confirmed to modulate the multidirectional differentiation of MSCs, while its effect on chondrogenic differentiation of Stem Cells from the Apical Papilla (SCAPs) is unknown. Here, we explored the effects and underlying mechanisms of betaine on chondrogenic differentiation of SCAPs. Methods Betaine was added for SCAPs chondrogenic induction. The chondrogenic differentiation potential was assessed using Alcian Blue staining, Sirius Red staining and the main chondrogenic markers. In vivo cartilage regeneration effects were evaluated by the rat TMJOA model. RNA-sequencing and biological analyses were performed to select target genes and biological processes involved. The mechanism betaine acts on chondrogenic differentiation of SCAPs was further explored. Results Betain-treated SCAPs demonstrated stronger cartilage regeneration in vitro and promoted cartilage repair of TMJOA in vivo. Betaine enhanced the expression of WDR81 in SCAPs during chondrogenesis. WDR81 overexpression promoted chondrogenic differentiation of SCAPs, while WDR81 depletion inhibited chondrogenic differentiation. In addition, both betaine treatment and WDR81 overexpression reduced intracellular reactive oxygen species levels and increased mitochondrial membrane potential in SCAPs. Conclusion Betaine promotes SCAPs chondrogenic differentiation and provided an effective candidate for TMJOA treatment. WDR81 may serve as the potential drug target through mitophagy.
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series Stem Cell Research & Therapy
spelling doaj-art-217593feca3c49be87e1434801241ab92025-02-09T12:15:50ZengBMCStem Cell Research & Therapy1757-65122025-02-0116111610.1186/s13287-025-04161-4Betaine enhances SCAPs chondrogenic differentiation and promotes cartilage repair in TMJOA through WDR81Meiyue Wang0Zejie Wu1Xiaoyu Zheng2Yishu Huang3Yizhou Jin4Jiaxin Song5Wanzhen Lei6Hua Liu7Riyue Yu8Haoqing Yang9Runtao Gao10Department of Stomatology, Beijing Friendship Hospital, Capital Medical UniversityDepartment of Stomatology, Beijing Friendship Hospital, Capital Medical UniversityDepartment of Stomatology, Beijing Friendship Hospital, Capital Medical UniversityBeijing Laboratory of Oral Health, Capital Medical UniversityBeijing Laboratory of Oral Health, Capital Medical UniversityBeijing Laboratory of Oral Health, Capital Medical UniversityBeijing Laboratory of Oral Health, Capital Medical UniversityBeijing Laboratory of Oral Health, Capital Medical UniversityDepartment of Stomatology, Beijing Shijitan Hospital, Capital Medical UniversityBeijing Laboratory of Oral Health, Capital Medical UniversityDepartment of Stomatology, Beijing Friendship Hospital, Capital Medical UniversityAbstract Background The cartilage tissue regeneration mediated with mesenchymal stem cells (MSCs) is considered as a viable strategy for temporomandibular joint osteoarthritis (TMJOA). Betaine has been confirmed to modulate the multidirectional differentiation of MSCs, while its effect on chondrogenic differentiation of Stem Cells from the Apical Papilla (SCAPs) is unknown. Here, we explored the effects and underlying mechanisms of betaine on chondrogenic differentiation of SCAPs. Methods Betaine was added for SCAPs chondrogenic induction. The chondrogenic differentiation potential was assessed using Alcian Blue staining, Sirius Red staining and the main chondrogenic markers. In vivo cartilage regeneration effects were evaluated by the rat TMJOA model. RNA-sequencing and biological analyses were performed to select target genes and biological processes involved. The mechanism betaine acts on chondrogenic differentiation of SCAPs was further explored. Results Betain-treated SCAPs demonstrated stronger cartilage regeneration in vitro and promoted cartilage repair of TMJOA in vivo. Betaine enhanced the expression of WDR81 in SCAPs during chondrogenesis. WDR81 overexpression promoted chondrogenic differentiation of SCAPs, while WDR81 depletion inhibited chondrogenic differentiation. In addition, both betaine treatment and WDR81 overexpression reduced intracellular reactive oxygen species levels and increased mitochondrial membrane potential in SCAPs. Conclusion Betaine promotes SCAPs chondrogenic differentiation and provided an effective candidate for TMJOA treatment. WDR81 may serve as the potential drug target through mitophagy.https://doi.org/10.1186/s13287-025-04161-4Chondrogenic differentiationStem cells from the apical papillaWDR81Temporomandibular joint osteoarthritisMitochondria
spellingShingle Meiyue Wang
Zejie Wu
Xiaoyu Zheng
Yishu Huang
Yizhou Jin
Jiaxin Song
Wanzhen Lei
Hua Liu
Riyue Yu
Haoqing Yang
Runtao Gao
Betaine enhances SCAPs chondrogenic differentiation and promotes cartilage repair in TMJOA through WDR81
Stem Cell Research & Therapy
Chondrogenic differentiation
Stem cells from the apical papilla
WDR81
Temporomandibular joint osteoarthritis
Mitochondria
title Betaine enhances SCAPs chondrogenic differentiation and promotes cartilage repair in TMJOA through WDR81
title_full Betaine enhances SCAPs chondrogenic differentiation and promotes cartilage repair in TMJOA through WDR81
title_fullStr Betaine enhances SCAPs chondrogenic differentiation and promotes cartilage repair in TMJOA through WDR81
title_full_unstemmed Betaine enhances SCAPs chondrogenic differentiation and promotes cartilage repair in TMJOA through WDR81
title_short Betaine enhances SCAPs chondrogenic differentiation and promotes cartilage repair in TMJOA through WDR81
title_sort betaine enhances scaps chondrogenic differentiation and promotes cartilage repair in tmjoa through wdr81
topic Chondrogenic differentiation
Stem cells from the apical papilla
WDR81
Temporomandibular joint osteoarthritis
Mitochondria
url https://doi.org/10.1186/s13287-025-04161-4
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