Periostin increased by mechanical stress upregulates interleukin‐6 expression in the ligamentum flavum

Abstract

Ligamentum flavum (LF) hypertrophy is a major cause of lumbar spinal canal stenosis. Although mechanical stress is thought to be a major factor involved in LF hypertrophy, the exact mechanism by which it causes hypertrophy has not yet been fully elucidated. Here, changes in gene expression due to long‐term mechanical stress were analyzed using RNA‐seq in a rabbit LF hypertrophy model. In combination with previously reported analysis results, periostin was identified as a molecule whose expression fluctuates due to mechanical stress. The expression and function of periostin were further investigated using human LF tissues and primary LF cell cultures. Periostin was abundantly expressed in human hypertrophied LF tissues, and periostin gene expression was significantly correlated with LF thickness. In vitro, mechanical stress increased gene expressions of periostin, transforming growth factor‐β1, α‐smooth muscle actin, collagen type 1 alpha 1, and interleukin‐6 (IL‐6) in LF cells. Periostin blockade suppressed the mechanical stress‐induced gene expression of IL‐6 while periostin treatment increased IL‐6 gene expression. Our results suggest that periostin is upregulated by mechanical stress and promotes inflammation by upregulating IL‐6 expression, which leads to LF degeneration and hypertrophy. Periostin may be a pivotal molecule for LF hypertrophy and a promising therapeutic target for lumbar spinal stenosis.

Evaluation of differences in expression pattern of three isoforms of the transforming growth factor beta in patients with lumbosacral stenosis

“…Therefore, it appears that TGF-β-1 is the dominant factor contributing to the remodeling of the ligamentum flavum, which involves replacing elastin fibers with collagen fibers [ 47–49 ]. Also, Yabu et al [ 50 ] noted an increase in the expression of TGF-β 1, IL-6, α –smooth muscle actin and collagen type 1 alpha in the hypertrophied ligaments flavum of the L/S spine, indicating the significant involvement of signaling pathways dependent on from IL-6 [ 50 ].…”

Vertebral Subluxation and Systems Biology: An Integrative Review Exploring the Salutogenic Influence of Chiropractic Care on the Neuroendocrine-Immune System

“…Interleukins, like IFNs, are therefore effector molecules with diverse functions within the NEI supersystem. Biologically, the flux of interleukins can be affected directly by spinal interventions via simple biomechanical stress [ 286 , 287 ] or may be altered by the presence or change of the inflammatory state of the vertebral motion segment [ 288 , 289 ].…”

Nonsurgical therapy for lumbar spinal stenosis caused by ligamentum flavum hypertrophy: A review

“…Chronic inflammation, mediated by inflammatory mediators such as IL-6, IL-1β, and TNF-α, is considered a significant factor contributing to LFH, [50] the search for therapeutic targets to regulate inflammation in LF is imperative, among which periostin may become a new potential anti-inflammatory target. Periostin is an extracellular matrix (ECM) protein, and Akito et al [51] discovered that overexpression of periostin increased the expression of IL-6 in human and rabbit LF, whereas inhibition of periostin decreased the expression of IL-6. Periostin may also play a role in transforming LF cells into myofibroblasts and in overexpressing collagen, which are key factors leading to histological changes in LFH.…”