MicroRNA-874-3p is a Potential Contributor to Primary Hyperparathyroidism-Induced Osteoporosis

Area of Science:

• Endocrinology
• Molecular Biology
• Bone Biology

Background:

• MicroRNA dysregulation is implicated in various bone diseases.
• The specific microRNAs contributing to primary hyperparathyroidism (PHPT)-induced osteoporosis are not well understood.

Purpose of the Study:

• To identify microRNAs involved in PHPT-induced osteoporosis.
• To investigate the role of miR-874-3p in the osteogenic differentiation of human mesenchymal stem cells (hMSCs).

Main Methods:

• High-throughput microRNA sequencing of parathyroid tissue from PHPT patients with or without osteoporosis.
• Quantitative real-time PCR (qRT-PCR) for microRNA verification.
• Gain- and loss-of-function assays in hMSCs to assess miR-874-3p's role in osteogenic differentiation.
• Dual luciferase reporter assays to confirm target interaction.

Main Results:

• Identified 32 upregulated and 18 downregulated microRNAs in PHPT osteoporosis patients.
• miR-874-3p was significantly upregulated in PHPT osteoporosis patients, parathyroid tissue, and peripheral blood extracellular vesicles of PHPT osteoporosis mice.
• Overexpression of miR-874-3p inhibited hMSC osteogenic differentiation and reduced osteogenic marker expression, while inhibition had the opposite effect.
• miR-874-3p was confirmed to bind to FTO.

Conclusions:

• miR-874-3p is upregulated in PHPT patients with osteoporosis.
• miR-874-3p suppresses osteogenic differentiation of hMSCs by targeting FTO.
• miR-874-3p plays a crucial role in the pathogenesis of PHPT-induced osteoporosis.