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Galectin-3 Induces a Pro-degradative/inflammatory Gene Signature in Human Chondrocytes, Teaming Up with Galectin-1 in Osteoarthritis Pathogenesis.
- Source :
-
Scientific reports [Sci Rep] 2016 Dec 16; Vol. 6, pp. 39112. Date of Electronic Publication: 2016 Dec 16. - Publication Year :
- 2016
-
Abstract
- Inflammatory chemo- and cytokines and matrix-degrading proteases underlie the progression of osteoarthritis (OA). Aiming to define upstream regulators for these disease markers, we pursued initial evidence for an upregulation of members of the adhesion/growth-regulatory galectin family. Immunohistochemical localization of galectin-3 (Gal-3) in sections of human cartilage with increasing levels of degeneration revealed a linear correlation reaching a chondrocyte positivity of 60%. Presence in situ was cytoplasmic, the lectin was secreted from OA chondrocytes in culture and binding of Gal-3 yielded lactose-inhibitable surface staining. Exposure of cells to the lectin led to enhanced gene expression and secretion of functional disease markers. Genome-wide transcriptomic analysis broadened this result to reveal a pro-degradative/inflammatory gene signature under the control of NF-κB. Fittingly, targeting this route of activation by inhibitors impaired the unfavourable response to Gal-3 binding, as also seen by shortening the lectin's collagen-like repeat region. Gal-3's activation profile overlaps with that of homodimeric galectin-1 (Gal-1) and also has distinctive (supplementing) features. Tested at subsaturating concentrations in a mixture, we found cooperation between the two galectins, apparently able to team up to promote OA pathogenesis. In summary, our results suggest that a network of endogenous lectins is relevant for initiating this process cascade.
- Subjects :
- Aged
Aged, 80 and over
Blood Proteins
Chondrocytes pathology
Extracellular Matrix metabolism
Female
Galectins
Gene Expression Profiling methods
Gene Expression Regulation
Humans
Male
Middle Aged
Oligonucleotide Array Sequence Analysis methods
Osteoarthritis genetics
Osteoarthritis immunology
Signal Transduction
Chondrocytes metabolism
Galectin 1 metabolism
Galectin 3 metabolism
Gene Regulatory Networks
Osteoarthritis pathology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 27982117
- Full Text :
- https://doi.org/10.1038/srep39112