Circ_0114581 promotes osteogenic differentiation of BMSCs via the MiR-155-5p/HNRNPA3 axis

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Osteoporosis (OP) is a prevalent metabolic bone disease marked by decreased bone mass and structural deterioration, increasing fracture risk.
• Discovering novel therapeutic targets is crucial for effective OP management.
• Competing endogenous RNA (ceRNA) networks, involving circular RNAs (circRNAs), are increasingly recognized for their roles in disease pathogenesis.

Purpose of the Study:

• To investigate the ceRNA mechanisms of circRNAs implicated in osteoporosis.
• To identify novel molecular players and regulatory pathways involved in OP development.

Main Methods:

• Analysis of OP-related high-throughput datasets to construct a ceRNA network.
• In vitro experiments using bone marrow-derived stem cells (BMSCs) to assess HNRNPA3 function.
• In vivo studies using ovariectomized mice models.
• Molecular biology techniques including miRNA mimics/inhibitors and circRNA overexpression vectors.
• Luciferase reporter assays to validate molecular interactions.

Main Results:

• HNRNPA3 was found to regulate osteogenic differentiation in BMSCs and its expression negatively correlated with OP in human and mouse bone tissues.
• miR-155-5p was identified as a negative regulator of HNRNPA3 expression.
• hsa_circ_0114581 was shown to promote HNRNPA3 expression and osteogenic differentiation by sponging miR-155-5p.
• Direct binding sites were confirmed between miR-155-5p and both HNRNPA3 and hsa_circ_0114581.

Conclusions:

• The hsa_circ_0114581/hsa-miR-155-5p/HNRNPA3 axis plays a significant role in the pathogenesis of osteoporosis.
• This axis represents a potential noncoding RNA-based therapeutic strategy for OP.
• The findings provide valuable insights into OP mechanisms and suggest novel biomarkers for future research.