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Betaine Downregulates RARRES1 to Alleviate Cartilage Fibrosis and Promote Hyaline Cartilage Repair
Shiqi Wang1, Yang Xue1, Jiarui Zhuang1
1Laboratory for Bone and Joint Disease, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, 321 Zhongshan Road, Nanjing 210008, China.
International Journal of Molecular Sciences
|August 13, 2026
Summary
Retinoic acid receptor responder 1 (RARRES1) is a biomarker for osteoarthritis cartilage fibrosis. Betaine alleviates fibrosis by downregulating RARRES1 and promoting reactive oxygen species (ROS) clearance via RGS2.
Area of Science:
- Biochemistry
- Molecular Biology
- Biomaterials Science
Background:
- Osteoarthritis (OA) is characterized by cartilage degeneration and irreversible fibrosis, compromising joint function.
- Current diagnostic and therapeutic strategies for cartilage fibrosis are limited.
- Identifying reliable biomarkers and therapeutic targets is crucial for managing OA progression.
Purpose of the Study:
- To identify key biomarkers associated with cartilage degeneration in osteoarthritis.
- To investigate the role of RARRES1 in cartilage fibrosis.
- To explore the therapeutic potential of betaine in mitigating cartilage fibrosis.
Main Methods:
- Bioinformatic analysis of RNA sequencing datasets (bulk and single-cell).
- In vitro chondrocyte fibrosis model induced by CTGF.
- siRNA-mediated gene knockdown of RARRES1.
- In vitro and in vivo experiments including Western blotting, functional assays, flow cytometry, and pathological staining.
Main Results:
- RARRES1 was identified as a key biomarker upregulated in OA cartilage and chondrocyte fibrosis models.
- Betaine treatment downregulated RARRES1 and promoted hyaline cartilage repair.
- RGS2 was identified as a critical mediator for betaine's ROS scavenging effects.
- Betaine inhibited RARRES1, upregulated RGS2, and cleared ROS, alleviating cartilage fibrosis.
Conclusions:
- RARRES1 is a significant biomarker for cartilage fibrosis in osteoarthritis.
- Betaine demonstrates therapeutic potential for cartilage fibrosis by modulating RARRES1 and ROS pathways.
- Targeting RARRES1 and ROS may offer novel strategies for treating osteoarthritis-related cartilage fibrosis.