• Richard A Wawrose, Anthony A Oyekan, Yunting Melissa Tang, Stephen R Chen, Joseph Chen, Brandon K Couch, Dong Wang, Peter G Alexander, Gwendolyn A Sowa, Nam V Vo, and Joon Y Lee.
• Ferguson Laboratory for Orthopedic and Spine Research, Department of Orthopedic Surgery, University of Pittsburgh, 200 Lothrop Street, E1643 Biomedical Science Tower, Pittsburgh, PA, 15261, USA.
• Eur Spine J. 2024 Mar 1; 33 (3): 892899892-899.

PurposeLumbar 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.MethodsLigamentum 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.ResultsWe 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.ConclusionThis 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.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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