MicroRNA-29a: a novel target for non-operative management of symptomatic lumbar spinal stenosis

• Published in: European spine journal 2024-03, Vol.33 (3), p.892-899
• Main Authors: Wawrose, Richard A., Oyekan, Anthony A., Tang, Yunting Melissa, Chen, Stephen R., Chen, Joseph, Couch, Brandon K., Wang, Dong, Alexander, Peter G., Sowa, Gwendolyn A., Vo, Nam V., Lee, Joon Y.
• Format: Article
• Language: English
• Subjects: Cauda Equina; Collagen Type I; Fibrosis; Gene expression; Humans; Hypertrophy; Medicine; Medicine & Public Health; MicroRNAs; MicroRNAs - genetics; miRNA; Morbidity; Neurosurgery; Neurosurgical Procedures; Original Article; Overexpression; Patients; Spinal cord; Spinal stenosis; Spinal Stenosis - therapy; Surgery; Surgical Orthopedics
• ISSN: 0940-6719; 1432-0932
• DOI: 10.1007/s00586-023-07671-y

Purpose Lumbar spinal stenosis (LSS) is the most common reason for spinal surgery in patients over the age of 65, and there are few effective non-surgical treatments. Therefore, the development of novel treatment or preventative modalities to decrease overall cost and morbidity associated with LSS is an urgent matter. The cause of LSS is multifactorial; however, a significant contributor is ligamentum flavum hypertrophy (LFH) which causes mechanical compression of the cauda equina or nerve roots. We assessed the role of a novel target, microRNA-29a (miR-29a), in LFH and investigated the potential for using miR-29a as a therapeutic means to combat LSS. Methods Ligamentum flavum (LF) tissue was collected from patients undergoing decompressive surgery for LSS and assessed for levels of miR-29a and pro-fibrotic protein expression. LF cell cultures were then transfected with either miR-29a over-expressor (agonist) or inhibitor (antagonist). The effects of over-expression and under-expression of miR-29a on expression of pro-fibrotic proteins was assessed. Results We demonstrated that LF at stenotic levels had a loss of miR-29a expression. This was associated with greater LF tissue thickness and higher mRNA levels of collagen I and III. We also demonstrated that miR29-a plays a direct role in the regulation of collagen gene expression in ligamentum flavum. Specifically, agents that increase miR-29a may attenuate LFH, while those that decrease miR-29a promote fibrosis and LFH. Conclusion This study demonstrates that miR-29a may potentially be used to treat LFH and provides groundwork to initiate the development of a therapeutic product for LSS.