Pitt Research Team Proposes MicroRNA-29a as a Novel Target for Non-operative Management of Symptomatic Lumbar Spinal Stenosis

June 29, 2023

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.

In this study out of the Ferguson Laboratory for Orthopaedic Spine Research, a research team from the University of Pittsburgh Departments of Physical Medicine and Rehabilitation and Orthopaedic Surgery discovered the role of a novel target, microRNA-29a (miR-29a), in modulating LFH and investigated the potential for using miR-29a as a therapeutic means to combat LSS.

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.

The team 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 the pro-fibrotic genes collagen I and III. They also demonstrated that miR29-a plays a direct role in the gene regulation of these collagens in ligamentum flavum. Specifically, agents that increase miR-29a may attenuate LFH, while those that decrease miR-29a promote fibrosis and LFH.

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.

Read the full study.

Research team

Richard Wawrose, MD

Anthony Oyekan, MD

Yunting Melissa Tang, MD

Stephen Chen, MD

Joseph Chen

Brandon Couch, MD

Dong Wang

Peter Alexander, PhD

Gwendolyn Sowa, MD, PhD

Nam Vo, PhD

Joon Lee, MD