Basic Study
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World J Stem Cells. May 26, 2023; 15(5): 490-501
Published online May 26, 2023. doi: 10.4252/wjsc.v15.i5.490
Stromal cell-derived factor-1α regulates chondrogenic differentiation via activation of the Wnt/β-catenin pathway in mesenchymal stem cells
Xiao Chen, Xia-Ming Liang, Jia Zheng, Yong-Hui Dong
Xiao Chen, Xia-Ming Liang, Jia Zheng, Yong-Hui Dong, Department of Orthopedics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou 450003, Henan Province, China
Author contributions: Chen X acquired the data; Zheng J and Dong YH designed the experiments; Chen X and Liang XM analyzed the data and wrote the manuscript; Liang XM and Chen X supervised the study; all authors read and approved the final manuscript.
Supported by Henan Provincial Natural Science Foundation of China, No. 212300410242; Youth Project Jointly Constructed by Henan Provincial Health Commission and the Ministry, No. SBGJ202103008; and Henan Young and Middle-aged Health Science and Technology Innovation Excellent Youth Talent Training Project of China, No. YXKC2021047.
Institutional review board statement: This study was approved by the Ethics Committee of the Henan Provincial People’s Hospital.
Institutional animal care and use committee statement: The animal study was approved by the Animal Experimentation Ethics Committee of Chongqing Western Biomedical Technology Co., Ltd.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Yong-Hui Dong, PhD, Professor, Department of Orthopedics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, No. 7 Weiwu Road, Jinshui District, Zhengzhou 450003, Henan Province, China.
Received: November 9, 2022
Peer-review started: November 9, 2022
First decision: December 25, 2022
Revised: January 21, 2023
Accepted: April 12, 2023
Article in press: April 12, 2023
Published online: May 26, 2023

Mesenchymal stem cells (MSCs) have been applied to treat degenerative articular diseases, and stromal cell-derived factor-1α (SDF-1α) may enhance their therapeutic efficacy. However, the regulatory effects of SDF-1α on cartilage differentiation remain largely unknown. Identifying the specific regulatory effects of SDF-1α on MSCs will provide a useful target for the treatment of degenerative articular diseases.


To explore the role and mechanism of SDF-1α in cartilage differentiation of MSCs and primary chondrocytes.


The expression level of C-X-C chemokine receptor 4 (CXCR4) in MSCs was assessed by immunofluorescence. MSCs treated with SDF-1α were stained for alkaline phosphatase (ALP) and with Alcian blue to observe differentiation. Western blot analysis was used to examine the expression of SRY-box transcription factor 9, aggrecan, collagen II, runt-related transcription factor 2, collagen X, and matrix metalloproteinase (MMP)13 in untreated MSCs, of aggrecan, collagen II, collagen X, and MMP13 in SDF-1α-treated primary chondrocytes, of glycogen synthase kinase 3β (GSK3β) p-GSK3β and β-catenin expression in SDF-1α-treated MSCs, and of aggrecan, collagen X, and MMP13 in SDF-1α-treated MSCs in the presence or absence of ICG-001 (SDF-1α inhibitor).


Immunofluorescence showed CXCR4 expression in the membranes of MSCs. ALP stain was intensified in MSCs treated with SDF-1α for 14 d. The SDF-1α treatment promoted expression of collagen X and MMP13 during cartilage differentiation, whereas it had no effect on the expression of collagen II or aggrecan nor on the formation of cartilage matrix in MSCs. Further, those SDF-1α-mediated effects on MSCs were validated in primary chondrocytes. SDF-1α promoted the expression of p-GSK3β and β-catenin in MSCs. And, finally, inhibition of this pathway by ICG-001 (5 µmol/L) neutralized the SDF-1α-mediated up-regulation of collagen X and MMP13 expression in MSCs.


SDF-1α may promote hypertrophic cartilage differentiation in MSCs by activating the Wnt/β-catenin pathway. These findings provide further evidence for the use of MSCs and SDF-1α in the treatment of cartilage degeneration and osteoarthritis.

Keywords: Stromal cell-derived factor-1α, Mesenchymal stem cells, Chondrogenic differentiation, Wnt/β-catenin, C-X-C chemokine receptor 4

Core Tip: In this study, we investigated the effect of stromal cell-derived factor-1α (SDF-1α) on the differentiation of bone marrow mesenchymal stem cells (MSCs) and primary chondrocytes in vitro. We demonstrated that SDF-1α promotes the chondrogenic differentiation of MSCs, and similar results were observed in primary chondrocytes. In addition, SDF-1α also activates the Wnt/β-catenin pathway to regulate chondrocyte hypertrophy and maturation in MSCs.