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

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