Effect of voluntary running activity on mRNA expression of extracellular matrix genes in a mouse model of intervertebral disc degeneration

Seon Ho Jang, Seunghwan Lee, Magali Millecamps, Alexander Danco, Hyung Mo Kang, Stéphanie Grégoire, Miyako Suzuki-Narita, Laura S. Stone

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Low back pain (LBP), a leading cause of global disability, is often associated with intervertebral disc degeneration (IDD). Exercise therapy is recommended for chronic LBP management and affects many tissues and organ systems. However, the ability of exercise to repair the extracellular matrix (ECM) in degenerating discs is unclear. The aims of the study were to examine mRNA expression of ECM structural components (collagen I, II, X, aggrecan) and regulators of matrix turnover (matrix metalloproteinases (MMP)-3, − 9, − 13, ADAMTS-4, − 5, TIMP1-4, CCN2) between age-matched (a) wild-type and secreted protein acidic and rich in cysteine (SPARC)-null, (b) sedentary and active, and (c) male and female mice. Methods: At 8 months of age, male and female SPARC-null and wild-type control mice received a home cage running wheel or a control, fixed wheel for 6 months. Deletion of the SPARC gene results in progressive IDD beginning at 2 to 4 months of age. Increased activity was confirmed, and qPCR was performed on excised lumbar discs. Results: Male SPARC-null mice expressed less aggrecan mRNA than wild-type controls. After 6 months of running, collagen, MMP3, and MMP13 expression was increased in male and MMP3 was increased in female SPARC-null mice. Sex differences were observed in wild-type mice and in response to IDD and long-term running. Conclusions: Voluntary running results in changes in mRNA consistent with increased ECM turnover and disc regeneration. Improved disc ECM might contribute to the beneficial effects of exercise on LBP and may create an intradiscal environment hospitable to regenerative therapies. Sex-specific differences should be considered in the development of disc-targeting therapies.

Original languageEnglish (US)
Article numbere1148
JournalJOR Spine
Volume4
Issue number3
DOIs
StatePublished - Sep 2021

Bibliographical note

Funding Information:
This work was supported by Canadian Institutes for Health Research grant MOP‐142291 to Laura S. Stone and Magali Millecamps. Seunghwan Lee was supported by the Catherine Bushnell postdoctoral fellowship from the Louise and Alan Edwards Foundation. The authors thank Dr Ji Zhang, Dr Luda Diatchenko, Dr Gris Pavel, and Dr Odile Neyret‐Djossou, the McGill University Comparative Medicine and Animal Resources Centre (CMARC), the Institut de recherches cliniques de Montréal (IRCM), and the Alan Edwards Centre for Research on Pain (AECRP) for support.

Funding Information:
This work was supported by Canadian Institutes for Health Research grant MOP-142291 to Laura S. Stone and Magali Millecamps. Seunghwan Lee was supported by the Catherine Bushnell postdoctoral fellowship from the Louise and Alan Edwards Foundation. The authors thank Dr Ji Zhang, Dr Luda Diatchenko, Dr Gris Pavel, and Dr Odile Neyret-Djossou, the McGill University Comparative Medicine and Animal Resources Centre (CMARC), the Institut de recherches cliniques de Montr?al (IRCM), and the Alan Edwards Centre for Research on Pain (AECRP) for support.

Publisher Copyright:
© 2021 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.

Keywords

  • degeneration
  • extracellular matrix
  • pain
  • pre-clinical models

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