TGF-β1 calcium signaling increases α5 integrin expression in osteoblasts

Leon J. Nesti, E. J. Caterson, Mark Wang, Richard Chang, Felix Chapovsky, Jan B. Hoek, Rocky S. Tuan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

TGF-β is a potent osteoactive factor and exhibits a wide variety of effects on osteoblasts, most of which are mediated through receptor associated Smad proteins. We have recently reported a novel TGF-β intracellular Ca2+ signaling pathway in osteoblasts, and found that this signaling is required for the TGF-β1 mediated enhancement of osteoblast adhesion to substrate. Given that interaction between the extracellular matrix protein fibronectin and α5β1 integrin on the cell surface is principally responsible for osteoblast substrate adhesion, we examined here whether the TGF-β1 stimulated Ca2+ signal is involved in this pathway. Our results show that, in primary human osteoblasts, the TGF-β1 induced intracellular Ca2+ signal is responsible, in part, for the stimulation of expression of α5 integrin, but not of β1 integrin or fibronectin. Increased levels of α5 integrin protein and mRNA were seen as early as 12 h after TGF-β1 treatment, but were inhibited by co-treatment of cells with nifedipine, a selective L-type Ca2+ channel blocker. TGF-β1 treatment increased both fibronectin and β1 integrin protein production within 48 h, in a manner unaffected by co-treatment with nifedipine. Immunofluorescence observations revealed that TGF-β1 treatment resulted in increased α5 integrin staining, and more prominent α5 integrin clustering, with increased co-localization with the actin cytoskeleton, effects that were blocked by co-treatment with nifedipine. The TGF-β1 induced intracellular Ca2+ signal in human osteoblasts is thus an important mechanistic step in the regulation of α5 integrin expression, later contributing to enhanced cell adhesion.

Original languageEnglish
Pages (from-to)1042-1049
Number of pages8
JournalJournal of Orthopaedic Research
Volume20
Issue number5
DOIs
StatePublished - 2002
Externally publishedYes

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