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

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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.

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Acknowledgments

We thank Jeremy D. Shaw and William F. Donaldson for their contributions. This work was supported by the Ferguson Laboratory of the University of Pittsburgh. Key words: ligamentum flavum, microRNA, lumbar spinal stenosis, spine, back pain.

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Authors and Affiliations

  1. 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

    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 & Joon Y. Lee

  2. Pittsburgh Ortho Spine Research (POSR) Group, Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA

    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 & Joon Y. Lee

  3. Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Gwendolyn A. Sowa

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  1. Richard A. Wawrose
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  2. Anthony A. Oyekan
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  3. Yunting Melissa Tang
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  7. Dong Wang
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Correspondence to Joon Y. Lee.

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The authors have no conflicts of interest to disclose. No competing interests or funding.

Ethical approvals

IRB approval was obtained through the University of Pittsburgh to complete this study (IRB #19070209).

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Wawrose, R.A., Oyekan, A.A., Tang, Y.M. et al. MicroRNA-29a: a novel target for non-operative management of symptomatic lumbar spinal stenosis. Eur Spine J 33, 892–899 (2024). https://doi.org/10.1007/s00586-023-07671-y

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  • DOI: https://doi.org/10.1007/s00586-023-07671-y

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