A comparative evaluation of the small leucine-rich proteoglycans of pathological human intervertebral discs

Abstract

Purpose Proteoglycans are important to the functioning of the intervertebral disc. In addition to aggrecan there are the small leucine-rich proteoglycans (SLRPs). These are less common but in other locations their functions include collagen organisation, sequestering growth factors and stimulating inflammation. We have performed a comparative analysis of the SLRP core protein species present in intervertebral discs with various pathologies. Methods Eighteen intervertebral discs from patients with scoliosis (n = 7, 19-53 years), degenerative disc disease (n = 6, 35-51 years) and herniations (n = 5, 33-58 years) were used in this study. Proteoglycans were dissociatively extracted from disc tissues and the SLRPs (biglycan, decorin, fibromodulin, keratocan and lumican) assessed by Western blotting following deglycosylation with chondroitinase ABC and keratanase.

Decorin inhibits the proliferation of HepG2 cells by elevating the expression of transforming growth factor-β receptor II

“…The current results showed that DCN transfection was able to significantly elevate the expression level of p15. Within cells, TGF-β binds with TGF-βRII to further phosphorylate TGF-βRI (18). The present study results showed that DCN transfection increased the expression level of TGF-βRII.…”

“…The TGF-β signaling pathway is able to inhibit the cell proliferation and differentiation at the early disease stage. However, at the later stage, TGF-β gradually loses its inhibitory effects, and thus promotes tumor metastasis (18). The present study results revealed that DCN enhanced TGF-βRII expression, promoting the TGF-β signaling pathway, which may represent the early event in the disease pathogenesis.…”

“…The signaling pathways involved in the action of DCN include the following: The regulation of the epidermal growth factor receptor (EGFR) and other ErbB family members, and the subsequent activation of the MAPK signaling pathway (10)(11)(12); the modulation of insulin-like growth factor receptor (IGFR) and low-density lipoprotein receptor-related protein 1, and the further activation of the phosphoinositide-3 kinase/protein kinase B/mammalian target of rapamycin pathway (13)(14)(15)(16); and the regulation of the transforming growth factor-β (TGF-β) pathway, including TGF-β1, TGF-β2, and TGF-β3 (17,18). In particular, the TGF-β signaling pathway serves different roles at different stages in the development of hepatic carcinoma.…”

Contaminants in commercial preparations of ‘purified’ small leucine-rich proteoglycans may distort mechanistic studies

“…Several SLRPs are known to occur in human discs and include biglycan, decorin, fibromodulin, keratocan and lumican [23–26]. In addition, some of these SLRPs have been shown to be increasingly fragmented with disc degeneration in humans [23], as well as in the discs of chondrodystrophoid breeds of dog, which are prone to disc disorders [27]. In addition to aggrecan, decorin and biglycan in particular have been shown to influence nerve growth and function.…”

Morphological changes in the human cervical intervertebral disc post trauma: response to fracture-type and degeneration grade over time

“…Although others report on similar processes such as fragmentation of certain SLRP (small leucine-rich proteoglycans) core proteins (e.g., bigylcans, lumican) in pathological tissues from patients with scoliosis, DDD and herniations, which are important for organization of collagen fibres and hence the structure of the extracellular matrix, the origin of these pathologies is different [25]. Moreover, there is evidence that these are involved in regulating inflammatory pathways [25]. Dudli et al reported on up-regulation of matrix remodelling genes being stable within 28 days following burst fractures in rabbits [26].…”