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- Title
MicroRNA-29a: a novel target for non-operative management of symptomatic lumbar spinal stenosis.
- 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.
- Abstract
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.
- Subjects
SPINAL stenosis; GENETIC regulation; CAUDA equina; PROTEIN expression; CELL culture
- Publication
European Spine Journal, 2024, Vol 33, Issue 3, p892
- ISSN
0940-6719
- Publication type
Article
- DOI
10.1007/s00586-023-07671-y