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Isolation of Mesenchymal Stem Cells from Human Alveolar Periosteum and Effects of Vitamin D on Osteogenic Activity of Periosteum-derived Cells
Published on: May 4, 2018
Inhibiting KCNMA1-AS1 promotes osteogenic differentiation of HBMSCs via miR-1303/cochlin axis
Yuan Lin1,2, Hanhao Dai2, Guoyu Yu1,3
1Department of Orthopedics, Fujian Provincial Hospital, Fuzhou, China.
Objective:
Osteoporosis is a progressive systemic skeletal disorder. Multiple profiling studies have contributed to characterizing biomarkers and therapeutic targets for osteoporosis. However, due to the limitation of the platform of miRNA sequencing, only a part of miRNA can be sequenced based on one platform.
Materials And Methods:
In this study, we performed miRNA sequencing in osteoporosis bone samples based on a novel platform Illumina Hiseq 2500. Bioinformatics analysis was performed to construct osteoporosis-related competing endogenous RNA (ceRNA) networks. Gene interference and osteogenic induction were used to examine the effect of identified ceRNA networks on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (HBMSCs).
Results:
miR-1303 was lowly expressed, while cochlin (COCH) and KCNMA1-AS1 were highly expressed in the osteoporosis subjects. COCH knockdown improved the osteogenic differentiation of HBMSCs. Meanwhile, COCH inhibition compensated for the suppression of osteogenic differentiation of HBMSCs by miR-1303 knockdown. Further, KCNMA1-AS1 knockdown promoted osteogenic differentiation of HBMSCs through downregulating COCH by sponging miR-1303.
Conclusions:
Our findings suggest that the KCNMA1-AS1/miR-1303/COCH axis is a promising biomarker and therapeutic target for osteoporosis.
Insights
This study identifies the KCNMA1-AS1/miR-1303/COCH axis as a key player in osteoporosis. Targeting this pathway shows potential for improving osteogenic differentiation in bone marrow stem cells.
Area of Science:
- Biomedical research
- Molecular biology
- Skeletal biology
Background:
- Osteoporosis is a systemic skeletal disorder with limited miRNA sequencing platforms.
- Previous studies identified biomarkers and therapeutic targets for osteoporosis.
- A comprehensive understanding of miRNA roles in osteoporosis requires advanced sequencing and network analysis.
Purpose of the Study:
- To investigate osteoporosis-related competing endogenous RNA (ceRNA) networks using a novel miRNA sequencing platform.
- To elucidate the role of identified ceRNA networks in the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (HBMSCs).
- To identify novel biomarkers and therapeutic targets for osteoporosis.
Main Methods:
- MiRNA sequencing on the Illumina Hiseq 2500 platform.
- Bioinformatics analysis to construct ceRNA networks.
- Gene interference and osteogenic induction assays in HBMSCs.
Main Results:
- miR-1303 was downregulated, while cochlin (COCH) and KCNMA1-AS1 were upregulated in osteoporosis subjects.
- COCH knockdown enhanced osteogenic differentiation of HBMSCs.
- KCNMA1-AS1 knockdown promoted osteogenic differentiation by downregulating COCH via sponging miR-1303.
Conclusions:
- The KCNMA1-AS1/miR-1303/COCH axis is identified as a significant regulatory pathway in osteoporosis.
- This axis serves as a potential biomarker for osteoporosis diagnosis.
- The KCNMA1-AS1/miR-1303/COCH axis represents a promising therapeutic target for osteoporosis treatment.
