MiR-23a-5p affects postmenopausal osteoporosis by targeting ALX3 to regulate osteoblast differentiation

• Published in: Journal of orthopaedic surgery and research Vol. 20; no. 1; pp. 700 - 12
• Main Authors: Zhang, Honghao, Rao, Wenjun, Lin, Rubing, Huang, Yingxuan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 25.07.2025; BioMed Central; BMC
• Subjects: Aged; ALX3; Animals; Bone Density - genetics; Cell Differentiation - genetics; Cell Differentiation - physiology; Development and progression; Estrogen; Female; Gene expression; Genes; Health aspects; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miR-23a-5p; Osteoblasts - metabolism; Osteoblasts - pathology; Osteoblasts - physiology; Osteogenesis - genetics; Osteogenic differentiation; Osteoporosis; Osteoporosis, Postmenopausal - genetics; Osteoporosis, Postmenopausal - metabolism; Osteoporosis, Postmenopausal - pathology; PMOP; Postmenopausal women; Rats; Rats, Sprague-Dawley; Risk factors; Transcription Factors - genetics; Transcription Factors - metabolism; ALX3; miR-23a-5p; PMOP; Osteogenic differentiation
• ISSN: 1749-799X; 1749-799X
• DOI: 10.1186/s13018-025-06133-z

Postmenopausal women are at an increased risk of developing osteoporosis (OP) due to a decline in estrogen levels. This study focuses on miR-23a-5p as the subject of investigation, aiming to elucidate its expression in postmenopausal osteoporosis (PMOP) and to explore its action mechanisms. A cohort of 150 postmenopausal women was recruited for this study, encompassing 78 participants diagnosed with OP and 72 controls without OP. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect gene expression levels. OVX rat model was established to simulate clinical features of estrogen deficiency to test the potential role of miR-23a-5p in PMOP. miR-23a-5p overexpression and knockdown MC3T3-E1 cell models were achieved to explore the underlying mechanisms through which miR-23a-5p influence PMOP. The expression of miR-23a-5p is upregulated in PMOP and it can distinguish OP patients from non-OP individuals. The expression of miR-23a-5p is related to bone mineral density (BMD) and is a risk factor for PMOP. miR-23a-5p affects serum bone turnover indicators and inhibits osteogenic differentiation marker expression in OVX rats. miR-23a-5p promotes PMOP by negatively regulating the expression of ALX homeobox 3 (ALX3) and affecting the osteogenic differentiation process of MC3T3-E1 cells. miR-23a-5p exhibits significantly elevated expression levels in PMOP and it might serve as a promising biomarker. miR-23a-5p plays a pivotal role in the progression of PMOP by negatively regulating ALX3 expression, thereby influencing the osteogenic differentiation process of MC3T3-E1 cells.