Galectins-1 and -3 in Human Intervertebral Disc Degeneration: Non-Uniform Distribution Profiles and Activation of Disease Markers Involving NF-κB by Galectin-1

J Orthop Res. 2019 Oct;37(10):2204-2216. doi: 10.1002/jor.24351. Epub 2019 Jun 24.

Abstract

Degeneration of the human intervertebral disc (IVD) is assumed to underlie severe clinical symptoms, in particular chronic back pain. Since adhesion/growth-regulatory galectins are linked to arthritis/osteoarthritis pathogenesis by activating a pro-degradative/-inflammatory gene expression signature, we hypothesized a similar functional involvement of galectins in IVD degeneration. Immunohistochemical evidence for the presence of galectins-1 and -3 in IVD is provided comparatively for specimens of spondylochondrosis, spondylolisthesis, and spinal deformity. Immunopositivity was detected in sections of fixed IVD specimens in each cellular compartment with age-, disease-, and galectin-type-related differences. Of note, presence of both galectins correlated with IVD degeneration, whereas correlation with age was seen only for galectin-3. In addition, staining profiles for these two galectins showed different distribution patterns in serial sections, an indication for non-redundant functionalities. In vitro, both galectins bound to IVD cells in a glycan-dependent manner. However, exclusively galectin-1 binding triggered a significant induction of functional disease markers (i.e., IL6, CXCL8, and MMP1/3/13) with involvement of the nuclear factor-kB pathway. This study thus gives direction to further network analyses and functional studies on galectins in IVD degeneration. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2204-2216, 2019.

Keywords: anulus fibrosus; degeneration; lectin; notochord; nucleus pulposus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / metabolism
  • Female
  • Galectin 1 / metabolism*
  • Galectin 3 / metabolism*
  • Humans
  • Intervertebral Disc Degeneration / metabolism*
  • Male
  • Middle Aged
  • NF-kappa B / metabolism*

Substances

  • Biomarkers
  • Galectin 1
  • Galectin 3
  • LGALS1 protein, human
  • NF-kappa B