Premium
Parathyroid hormone affects the fibroblast growth factor–proteoglycan signaling axis to regulate osteosarcoma cell migration
Author(s) -
Datsis Georgios A.,
Berdiaki Aikaterini,
Nikitovic Dragana,
Mytilineou Maria,
Katonis Pavlos,
Karamanos Nikos K.,
Tzanakakis George N.
Publication year - 2011
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2011.08300.x
Subject(s) - osteosarcoma , parathyroid hormone , fibroblast growth factor , microbiology and biotechnology , proteoglycan , hormone , medicine , chemistry , cancer research , endocrinology , biology , receptor , extracellular matrix , calcium
Parathyroid hormone (PTH)(1–34), which has been established to have a dual effect on bone metabolism, was recently found to regulate osteosarcoma cell migration. A significant part of the bone anabolic action of PTH(1–34) is attributed to fibroblast growth factor (FGF)‐2 stimulation. Furthermore, it was recently suggested that the FGF–proteoglycan axis may form an extracellular matrix‐related regulatory feedback loop that controls osteoblastic lineage cell proliferation and execution of the osteogenic program. In this study, we investigated the possible participation of FGF‐2 signaling in PTH(1–34)‐dependent osteosarcoma cell migration. FGF‐2 treatment of osteosarcoma cells resulted in a significant increase ( P ≤ 0.01) in MG63 cell migration, similar to that caused by PTH(1–34). mRNA expression analysis of cells treated with PTH(1–34) showed a strong increase in FGF‐2 transcript levels ( P = 0.0015). Interestingly, the addition of FGF‐2 to MG63 cells led to significant downregulation of small leucine‐rich proteoglycan biglycan expression at both the mRNA ( P ≤ 0.0001) and protein (60%) levels. In order to examine the significance of biglycan on MG63 cell migration, transfection with short interfering RNA specific for biglycan was performed, resulting in a significant increase ( P ≤ 0.01) in the migration capacity of biglycan‐deficient MG63 cells. In contrast, exogenous human recombinant biglycan strongly inhibited the migration of these cells ( P ≤ 0.01). Finally, a direct correlation between PTH(1–34) action and biglycan expression was established by the finding of a significant decrease ( P ≤ 0.01) in biglycan transcript levels in PTH(1–34)‐treated cells. To summarize, the present study demonstrates a novel cooperative mechanism of PTH(1–34) and FGF‐2 action that results in specific alteration of the biglycan extracellular matrix content to regulate osteosarcoma cell migration.