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Published on: April 26, 2024
miR-542-3p prevents ovariectomy-induced osteoporosis in rats via targeting SFRP1
Xiguang Zhang1, Yun Zhu2, Chuanlin Zhang1
1Department of Orthopedic Surgery, The People's Hospital of Yuxi City, The 6th Affiliated Hospital of Kunming Medical University, Yuxi, Yunan, China.
Abstract:
Secreted frizzled-related protein-1 (SFRP1) is a negative regulatory molecule of the WNT signaling pathway and serves as a therapeutic target for bone formation in osteoporosis. In this study, we first established an ovariectomized (OVX) rat model to simulate postmenopausal osteoporosis and found significant changes in miR-542-3p and sFRP1 expression by RNA sequencing and qRT-PCR. In addition, there was a significant negative correlation between miR-542-3p and sFRP1 mRNA levels in postmenopausal women with osteoporosis. We found that miR-542-3p inhibited the expression of sFRP1 mRNA by luciferase reporter assay. When the miR-542-3p binding site in sFRP1 3'UTR was deleted, it did not affect its expression. Western blot results showed that miR-542-3p inhibited the expression of SFRP1 protein. The expression of SFRP1 was significantly increased in osteoblast-induced mesenchymal stem cells (MSC), whereas the expression of miR-542-3p was significantly decreased. And miR-542-3p transfected MSCs showed a significant increase in osteoblast-specific marker expression, indicating that miR-542-3p is necessary for MSC differentiation. Inhibition of miR-542-3p reduced bone formation, confirmed miR-542-3p play a role in bone formation in vivo. In general, these data suggest that miR-542-3p play an important role in bone formation via inhibiting SFRP1 expression and inducing osteoblast differentiation.
Insights
MicroRNA-542-3p promotes bone formation by inhibiting secreted frizzled-related protein-1 (SFRP1) and enhancing osteoblast differentiation. This finding offers a new therapeutic target for osteoporosis treatment.
Area of Science:
- Molecular Biology
- Bone Biology
- Signaling Pathways
Background:
- Secreted frizzled-related protein-1 (SFRP1) negatively regulates WNT signaling and is a therapeutic target for bone formation.
- Osteoporosis, particularly postmenopausal osteoporosis, is characterized by impaired bone formation.
- MicroRNAs (miRNAs) are key regulators of gene expression with potential roles in bone metabolism.
Purpose of the Study:
- To investigate the role of miR-542-3p in bone formation and its relationship with SFRP1 in osteoporosis.
- To elucidate the mechanism by which miR-542-3p influences osteoblast differentiation and bone metabolism.
Main Methods:
- Established an ovariectomized (OVX) rat model to simulate postmenopausal osteoporosis.
- Utilized RNA sequencing, qRT-PCR, luciferase reporter assays, and Western blotting to analyze gene and protein expression.
- Investigated the effect of miR-542-3p on mesenchymal stem cell (MSC) differentiation and bone formation in vivo.
Main Results:
- Downregulation of miR-542-3p and upregulation of SFRP1 were observed in OVX rats and postmenopausal women with osteoporosis.
- miR-542-3p directly inhibits SFRP1 expression at both mRNA and protein levels.
- miR-542-3p promotes osteoblast differentiation and enhances bone formation in vivo.
Conclusions:
- miR-542-3p plays a critical role in bone formation by suppressing SFRP1 and promoting osteoblast differentiation.
- The miR-542-3p/SFRP1 axis represents a potential therapeutic strategy for treating osteoporosis.
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