TGF-β1-stimulated osteoblasts require intracellular calcium signaling for enhanced α5 integrin expression

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

18 Scopus citations

Abstract

The osteoactive factor, transforming growth factor β1 (TGF-β1), infuences osteoblast activity and bone function. We recently characterized a Smad-independent TGF-β1-induced Ca2+ signal in human osteoblasts (HOB) and demonstrated its importance in cell adhesion. Here, we further elucidate the role of the TGF-β1 Ca2+ signal in the mechanics of HOB adhesion. Osteoblast interaction with fibronectin (FN) through α5β1 integrin is principally responsible for osteoblast-substrate adhesion. Our results show that the TGF-β1 intracellular Ca2+ signal is responsible, in part, for stimulation of α5 integrin expression, but not β1 integrin or FN expression. Increased α5 integrin protein and mRNA expression was seen as early as 12 h after TGF-β1 treatment, but was inhibited by cotreatment with nifedipine, a Ca2+ channel blocker. TGF-β1 increased both FN and β1 integrin protein production within 48 h, independent of nifedipine cotreatment. Immunofluorescence observations revealed that TGF-β1 increased α5 integrin staining, clustering, and colocalization with the actin cytoskeleton, effects that were blocked by nifedipine. The TGF-β1 Ca2+ signal, a pathway crucial for HOB adhesion, enhances α5 integrin expression, focal contact formation, and cytoskeleton reorganization. These early events are necessary for osteoblast adhesion; thus they determine the fate of the cell and ultimately affect bone function.

Original languageEnglish
Pages (from-to)178-182
Number of pages5
JournalAnnals of the New York Academy of Sciences
Volume961
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Orthopedic tissue engineering
  • Signaling
  • TGF-β

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