Upregulation of microRNA-96-5p is associated with adolescent idiopathic scoliosis and low bone mass phenotype

Abstract

Bone densitometry revealed low bone mass in patients with adolescent idiopathic scoliosis (AIS) and its prognostic potential to predict curve progression. Recent studies showed differential circulating miRNAs in AIS but their diagnostic potential and links to low bone mass have not been well-documented. The present study aimed to compare miRNA profiles in bone tissues collected from AIS and non-scoliotic subjects, and to explore if the selected miRNA candidates could be useful diagnostic biomarkers for AIS. Microarray analysis identified miR-96-5p being the most upregulated among the candidates. miR-96-5p level was measured in plasma samples from 100 AIS and 52 healthy girls. Our results showed significantly higher plasma levels of miR-96-5p in AIS girls with an area under the curve (AUC) of 0.671 for diagnostic accuracy. A model that was composed of plasma miR-96-5p and patient-specific parameters (age, body weight and years since menarche) gave rise to an improved AUC of 0.752. Ingenuity Pathway Analysis (IPA) indicated functional links between bone metabolic pathways and miR-96-5p. In conclusion, differentially expressed miRNAs in AIS bone and plasma samples represented a new source of disease biomarkers and players in AIS etiopathogenesis, which required further validation study involving AIS patients of both genders with long-term follow-up.

Investigating the Differential Circulating microRNA Expression in Adolescent Females with Severe Idiopathic Scoliosis: A Proof-of-Concept Observational Clinical Study

“…Moreover, some of them were already known for their involvement in cell signaling pathways that controlled the pluripotency of stem cells, such as the Wnt/β-catenin pathway [ 22 ]. Other studies compared data from differentially expressed miRNAs on bone tissues with the plasma levels of the selected miRNAs candidates, to develop a composite diagnostic model for AIS [ 50 ]. Overexpression of miR-151a-3p in primary osteoblasts from severe AIS patients negatively affected bone homeostasis, and the high plasma expression levels suggested miR-151a-3p as a potential biomarker for severe AIS.…”

“…In this regard, Zang et al also showed a significant negative correlation between circulating miR-145 levels and serum sclerostin, osteopontin, and osteoprotegerin in AIS [ 26 ]. As shown by Chen et al, the analysis of differentially expressed miRNAs in AIS bone and plasma samples represents a new source of biomarkers and actors in the aetiopathogenesis of AIS; for example, miRNA profiles in bone tissues from AIS and healthy controls identified the upregulation of miR-96-5p, which was further confirmed in plasma samples from AIS girls compared to HC [ 50 ].…”

Research progress on the regulation of bone marrow stem cells by noncoding RNAs in adolescent idiopathic scoliosis

“…Subsequently, a model was constructed using plasma miR‐96‐5p levels and patient‐specific parameters (age, weight, and years since menarche), which increased the AUC to 0.752. Furthermore, the original pathway analysis indicated a functional relationship between the bone metabolism pathway and miR‐96‐5p (Chen et al, 2022).…”

Advances in epigenetic research of adolescent idiopathic scoliosis and congenital scoliosis

“…miR-151a-3p could be used as a biomarker to predict severe AIS. In 2022, Chen et al evaluated four patients with severe AIS and four age-matched controls ( Chen et al, 2022 ); in this study, they extracted intraoperative iliac spine bone tissue for RNA microarray analysis. miR-96-5p expression was significantly higher in patients with AIS.…”