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Chondrogenic Differentiation Induction of Adipose-derived Stem Cells by Centrifugal Gravity
Published on: February 24, 2017
circRNA-ZCCHC14 affects the chondrogenic differentiation ability of peripheral blood-derived mesenchymal stem cells
Daohong Zhao1, Hong Chen2, Jia Zhong3
1Department of Orthopaedics, The Second Affiliated Hospital of Kunming Medical University, Kunming, China. 381454239@qq.com.
Abstract:
circRNAs play an important role in the progression of osteoarthritis (OA). Therefore, we aimed to reveal the mechanism of action of circRNA-ZCCHC14 in OA. OA animal and cell models were constructed, and clinical samples were collected. The expression of circRNA-ZCCHC14 and miR-181a was detected by RT‒qPCR. The chondrogenic differentiation ability of peripheral blood-derived mesenchymal stem cells (PBMSCs) was detected by Alcian blue staining. The expression of chondrogenic differentiation-related proteins was detected by Western blotting. Double fluorescein experiments verified the targeting relationship of miR-181a with circRNA-ZCCHC14 and GREM1. Upregulation of circRNA-ZCCHC14 was observed in blood, in BMP-2- and TGF-β3-treated PBMSCs from OA patients and in animal models. Knockdown of circRNA-ZCCHC14 promoted the chondrogenic differentiation ability of PBMSCs. circRNA-ZCCHC14 was found to bind to miR-181a and negatively regulate miR-181a expression. Inhibition of miR-181a reversed the promoting effect of circRNA-ZCCHC14 knockdown on the chondrogenic differentiation ability of PBMSCs. GREM1 was identified as a target of miR-181a. Overexpression and knockdown of GREM1 regulated the expression of BMP2, which in turn affected the chondrogenic differentiation ability of PBMSCs, indicating that GREM1 and BMP2 have antagonistic effects and that they jointly regulate the chondrogenic differentiation of PBMSCs. circRNA-ZCCHC14 may promote the chondrogenic differentiation ability of PBMSCs by regulating miR-181a and inhibiting the expression of GREM1.
Insights
Circular RNA ZCCHC14 promotes osteoarthritis progression by inhibiting miR-181a and GREM1, impairing chondrogenic differentiation of mesenchymal stem cells.
Area of Science:
- Biochemistry
- Molecular Biology
- Orthopedics
Background:
- Osteoarthritis (OA) is a degenerative joint disease where circular RNAs (circRNAs) are implicated in its progression.
- Understanding the specific mechanisms of circRNAs in OA pathogenesis is crucial for developing targeted therapies.
Purpose of the Study:
- To elucidate the role and mechanism of circRNA-ZCCHC14 in osteoarthritis (OA).
- To investigate the regulatory pathway involving circRNA-ZCCHC14, miR-181a, and GREM1 in chondrogenesis.
Main Methods:
- Construction of OA animal and cell models, collection of clinical samples.
- RT-qPCR for gene expression analysis, Western blotting for protein analysis.
- Alcian blue staining for chondrogenic differentiation, dual-luciferase reporter assays for target validation.
Main Results:
- CircRNA-ZCCHC14 was upregulated in OA patient samples and models.
- Knockdown of circRNA-ZCCHC14 enhanced chondrogenic differentiation of peripheral blood-derived mesenchymal stem cells (PBMSCs).
- CircRNA-ZCCHC14 targets miR-181a, which in turn targets GREM1; GREM1 and BMP2 showed antagonistic effects on chondrogenesis.
Conclusions:
- CircRNA-ZCCHC14 promotes OA by inhibiting miR-181a and consequently upregulating GREM1.
- This pathway negatively impacts the chondrogenic differentiation of PBMSCs, highlighting circRNA-ZCCHC14 as a potential therapeutic target in OA.
