2. Academic Validation
  3. Betaine enhances SCAPs chondrogenic differentiation and promotes cartilage repair in TMJOA through WDR81

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

  • Stem Cell Res Ther. 2025 Feb 7;16(1):55. doi: 10.1186/s13287-025-04161-4.
Meiyue Wang 1,  Zejie Wu 1,  Xiaoyu Zheng 1,  Yishu Huang 2,  Yizhou Jin 2,  Jiaxin Song 2,  Wanzhen Lei 2,  Hua Liu 2,  Riyue Yu 3,  Haoqing Yang 4 5,  Runtao Gao 6
Affiliations

Affiliations

  • 1 Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
  • 2 Beijing Laboratory of Oral Health, Capital Medical University, Beijing, 100050, China.
  • 3 Department of Stomatology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100050, China. yu-riyue@bjsjth.cn.
  • 4 Beijing Laboratory of Oral Health, Capital Medical University, Beijing, 100050, China. yanghaoqing@mail.ccmu.edu.cn.
  • 5 Research Unit of Tooth Development and Regeneration, Chinese Academy of Medical Sciences, Beijing, 100050, China. yanghaoqing@mail.ccmu.edu.cn.
  • 6 Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China. gaoruntao@ccmu.edu.cn.
PMID: 39920811 DOI: 10.1186/s13287-025-04161-4
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.

Keywords

Chondrogenic differentiation; Mitochondria; Stem cells from the apical papilla; Temporomandibular joint osteoarthritis; WDR81.

Figures
Products
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  • HY-D0985A
    98.70%, Mitochondrial Membrane Potential Fluorescent Dye