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Published on: March 18, 2019
MiR-99b-5p suppressed proliferation of human osteoblasts by targeting FGFR3 in osteoporosis
Muliang Ding1, Bo Liu1, Xia Chen1
1Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, 410001, Hunan, China.
Abstract:
Osteoporosis is a common skeletal disease characterized by reduced bone mass partially caused by an imbalance between bone resorption and formation. Considering the potential role of microRNAs (miRNAs) in osteoporosis, we attempted to identify deregulated miRNA that participates in the pathogenesis of osteoporosis. We analyzed online datasets for differentially expressed miRNAs and predicted deregulated miRNA target genes, applied these genes for signaling pathway enrichment annotation, and selected the possible miR-99b-5p/FGFR3 axis. Within osteoporosis bone tissues, miR-99b-5p was upregulated and FGFR3 was downregulated. miR-99b-5p overexpression inhibited osteoblast proliferation and osteogenesis-related genes expression, whereas FGFR3 overexpression exerted opposite effects upon the proliferation of osteoblasts and osteogenesis-related genes expression. By direct targeting, miR-99b-5p inhibited FGFR3 expression. Moreover, FGFR3 silencing significantly reversed the roles of miR-99b-5p inhibition in the proliferation of osteoblasts and osteogenesis-related genes expression. In conclusion, we identify a deregulated miRNA/mRNA axis in osteoporosis and osteogenic differentiation, namely the miR-99b-5p/FGFR3 axis; through targeting FGFR3, miR-99b-5p inhibits osteoblast proliferation and activity, which might subsequently affect the bone formation in osteoporosis progression.
Insights
MicroRNAs (miRNAs) play a role in osteoporosis. This study identifies the miR-99b-5p/FGFR3 axis, where miR-99b-5p targets FGFR3, inhibiting osteoblast activity and potentially impacting bone formation in osteoporosis.
Area of Science:
- Biomedical Science
- Molecular Biology
- Skeletal Biology
Background:
- Osteoporosis is a skeletal disease marked by decreased bone mass, stemming from imbalanced bone resorption and formation.
- MicroRNAs (miRNAs) are increasingly recognized for their potential involvement in osteoporosis pathogenesis.
Purpose of the Study:
- To identify deregulated miRNAs implicated in osteoporosis.
- To elucidate the functional role of the identified miRNA/mRNA axis in osteoblast activity and bone formation.
Main Methods:
- Analysis of online datasets for differentially expressed miRNAs in osteoporosis.
- Prediction and pathway enrichment analysis of miRNA target genes.
- In vitro experiments assessing the effects of miR-99b-5p and FGFR3 on osteoblast proliferation and gene expression.
- Validation of direct targeting and functional reversal experiments.
Main Results:
- The miR-99b-5p/FGFR3 axis was identified as a key player in osteoporosis.
- miR-99b-5p was upregulated, while FGFR3 was downregulated in osteoporosis bone tissues.
- miR-99b-5p overexpression inhibited osteoblast proliferation and osteogenesis, whereas FGFR3 overexpression promoted them.
- miR-99b-5p directly targets and inhibits FGFR3, impacting osteoblast function.
Conclusions:
- The miR-99b-5p/FGFR3 axis is a critical regulator of osteoblast proliferation and activity in osteoporosis.
- Targeting FGFR3 by miR-99b-5p contributes to reduced bone formation in osteoporosis progression.
- This axis represents a potential therapeutic target for osteoporosis treatment.
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