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Chondrogenic Differentiation Induction of Adipose-derived Stem Cells by Centrifugal Gravity
Published on: February 24, 2017
Long non-coding RNA CIR inhibits chondrogenic differentiation of mesenchymal stem cells by epigenetically suppressing
Feng Liu1,2, De-Ye Song1, Jun Huang1
1Department of Orthopedics, The Second Xiangya Hospital of Central South University, No.139 Renminzhong Road, Changsha, 410011, Hunan, People's Republic of China.
Background:
Osteoarthritis (OA) is the most common articular disorder, leading to joint malfunction and disability. Although the incidence of OA is increasing globally, the treatment of OA is very limited. LncRNA CIR has been implicated in OA through unclear mechanisms. Here, we investigated the role of lncRNA CIR in chondrogenic differentiation.
Methods:
Human umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) were obtained from human umbilical cords. Flow cytometry was used to analyze the surface markers of hUC-MSCs. Various culture conditions and corresponding staining assays were employed to assess the differentiation abilities of hUC-MSC. qRT-PCR, western blot, and immunostaining were used to measure expression levels of related genes and proteins such as lncRNA CIR, ATOH8, EZH2, and H3K27me3. RNA immunoprecipitation assay, biotin pull-down, and chromatin immunoprecipitaion assay were performed to analyze the interactions of lncRNA CIR, EZH2, H3K27me3 and ATOH8 promoter.
Results:
hUC-MSCs exhibited MSCs features and could differentiate into chondrocytes under specific conditions. LncRNA CIR was downregulated while ATOH8 was upregulated during the chondrogenic differentiation of hUC-MSCs. Knockdown lncRNA CIR or overexpression of ATOH8 promoted chondrogenic differentiation. Further, lncRNA CIR bound to EZH2 and repressed ATOH8 expression via EZH2-mediated H3K27me3, which promotes the methylation of ATOH8. Inhibition of ATOH8 reversed the effects of knockdown lncRNA CIR on chondrogenic differentiation.
Conclusion:
LncRNA CIR suppresses chondrogenic differentiation of hUC-MSCs. Mechanistically, lncRNA CIR could inhibit ATOH8 expression that functions to promote chondrogenic differentiation through EZH2-mediated epigenetic modifications.
Insights
Long non-coding RNA CIR (lncRNA CIR) suppresses chondrogenic differentiation in human umbilical cord mesenchymal stem cells (hUC-MSCs). It inhibits ATOH8 expression through epigenetic modifications, impacting osteoarthritis treatment strategies.
Area of Science:
- Biochemistry
- Cell Biology
- Epigenetics
Background:
- Osteoarthritis (OA) is a prevalent joint disorder with limited therapeutic options.
- The role of long non-coding RNA CIR (lncRNA CIR) in OA pathogenesis remains unclear.
- Investigating lncRNA CIR's function in chondrogenic differentiation is crucial for understanding OA.
Purpose of the Study:
- To elucidate the role of lncRNA CIR in chondrogenic differentiation of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs).
- To determine the molecular mechanism by which lncRNA CIR influences chondrogenesis.
Main Methods:
- Isolation and characterization of hUC-MSCs.
- Assessment of chondrogenic differentiation potential.
- Analysis of gene and protein expression using qRT-PCR, Western blot, and immunostaining.
- Investigation of molecular interactions via RNA immunoprecipitation, biotin pull-down, and chromatin immunoprecipitation assays.
Main Results:
- LncRNA CIR expression decreased while ATOH8 expression increased during hUC-MSC chondrogenic differentiation.
- Knockdown of lncRNA CIR or overexpression of ATOH8 promoted chondrogenesis.
- LncRNA CIR binds to EZH2, repressing ATOH8 expression through EZH2-mediated H3K27me3 epigenetic modification.
- Inhibition of ATOH8 reversed the pro-chondrogenic effects of lncRNA CIR knockdown.
Conclusions:
- LncRNA CIR acts as a suppressor of chondrogenic differentiation in hUC-MSCs.
- LncRNA CIR inhibits ATOH8, a key promoter of chondrogenesis, via EZH2-mediated epigenetic silencing.
- This mechanism highlights lncRNA CIR as a potential therapeutic target for OA.
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