Glycosaminoglycan Metabolism and Cytokine Release in Normal and Otosclerotic Human Bone Cells Interleukin-1 Treated

Abstract

Glycosaminoglycans (GAGs), normal components of the extracellular matrix (ECM), and the glycosidases, that degrade them, play a key role in the bone remodelling process. The effects of interleukin-1 alpha (IL-1 alpha) on GAG metabolism in normal and otosclerotic human bone cells as well as its capacity to modulate IL-1 alpha, IL-1 beta and IL-6 secretion in both populations was analyzed. The amount of radiolabeled GAGs was lower in otosclerotic than in normal bone cells. IL-1 alpha reduced newly synthesized cellular and extracellular GAGs in normal cells, but only those of the cellular compartment in otosclerotic bone cells. It depressed heparan sulphate (HS) more in normal cells and chondroitin sulphate (CS) more in otosclerotic bone cells. The HA/total sulphated GAG ratio was shifted in favour of the latter in otosclerotic cells, whereas the opposite effect was seen after IL-1 alpha treatment. There was little difference in the beta-D-glucuronidase levels of the normal and pathological cells, while beta-N-acetyl-D-glucosaminidase was significantly increased in otosclerotic bone cells. As the activity of neither enzyme was modified by treatment with IL-1 alpha, the cytokine seems to exert its influences on GAG synthesis rather than on the degradation process. IL-1 alpha, IL-1 beta and IL-6 secretion was markedly higher in otosclerotic cells. IL-1 alpha modulated the secretion of each interleukin differently, thus resulting in a cytokine cascade that may act in autocrine/paracrine manner on target cells. The authors suggest that changes in the cytokine network may have a specific, yet still unknown, role during normal and pathological osteogenesis.

Apert p.Ser252Trp Mutation in FGFR2 Alters Osteogenic Potential and Gene Expression of Cranial Periosteal Cells

“…We also found downregulation of most of the genes involved in cell adhesion (11 out of 13 genes) and extracellular matrix composition (five out of seven genes) in AS cells, which contrast one previous study that has shown that periosteal AS cells synthesize a greater amount of extracellular matrix components (including glycosaminoglycans, type I and III collagens, and fibronectin) than normal cells (28). In view of this, it would be interesting to test if the suggested reduction in cell adhesion and extracellular matrix complexity of our AS periosteal cells are associated with the greater osteogenic capacity of these cells.…”

Glycosaminoglycan profile in macrophages exposed to Candida albicans and interleukins

“…Furthermore we, like others [48][49][50][51][52], have shown that macrophage-derived growth factors are able to modulate the function of normal and pathological fibroblasts affecting collagen and GAG synthesis and driving the fibro-proliferative responses. Therefore, ECM components become the modulatory signals of a microenvironment, where they modulate the genetic program and control the cytokine release responsible for the fibrotic processes of many connective disorders.…”

CCL20/CCR6 chemokine/receptor expression in bone tissue from osteoarthritis and rheumatoid arthritis patients: Different response of osteoblasts in the two groups

“…In fact, CCL20 induces a significant increase of b-Nacetylhexosaminidase in osteoblasts from OA patients and induces proliferation in osteoblasts from RA patients. OA subchondral bone is characterized by fibrosis, and b-N-acetylhexosaminidase is an enzyme involved in the degradation of glycosaminoglycans and highly expressed by osteosclerotic osteoblasts (Bodo et al, 1997). CCL20 seems to contribute to ECM-bone remodeling in OA and to the induction of osteoblast proliferation in RA.…”