Smad1 domains interacting with Hoxc-8 induce osteoblast differentiation

Xiangli Yang, Xiaohui Ji, Xing Ming Shi, Xu Cao

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Bone morphogenetic proteins are potent osteotropic agents that induce osteoblast differentiation and bone formation. The signal transduction of bone morphogenetic proteins has recently been discovered to involve Smad proteins. Smad1 is an essential intracellular component that is specifically phosphorylated by bone morphogenetic protein receptors and translocated into the nucleus upon ligand stimulation. Previously, we have reported that Smad1 activates osteopontin gene expression in response to bone morphogenetic protein simulation through an interaction with a homeodomain transcription factor, Hoxc-8. In the present study, the interaction domains between the two proteins were characterized by deletional analysis in both yeast two-hybrid and gel shift assays. Two regions within the amino-terminal 87 amino acid residues of Smad1 were mapped to interact with Hoxc-8, one of which binds to the homeodomain. Overexpression of recombinant cDNAs encoding the Hoxc-8 interaction domains of Smad1 effectively activated osteopontin gene transcription in transient transfection assays. Furthermore, stable expression of these Smad1 fragments in 2T3 osteoblast precursor cells stimulated osteoblast differentiation-related gene expression and led to mineralized bone matrix formation. Our data suggest that the interaction of amino-terminal Smad1 with Hoxc-8 mimics bone morphogenetic protein signaling and is sufficient to induce osteoblast differentiation and bone cell formation.

Original languageEnglish (US)
Pages (from-to)1065-1072
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number2
DOIs
StatePublished - Jan 14 2000
Externally publishedYes

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Bone Morphogenetic Proteins
Osteoblasts
Osteogenesis
Bone
Osteopontin
Gene expression
Assays
Bone Morphogenetic Protein Receptors
Smad Proteins
Gene Expression
Signal transduction
Bone Matrix
Transcription
Yeast
Transfection
Cell Differentiation
Signal Transduction
Transcription Factors
Complementary DNA
Genes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Smad1 domains interacting with Hoxc-8 induce osteoblast differentiation. / Yang, Xiangli; Ji, Xiaohui; Shi, Xing Ming; Cao, Xu.

In: Journal of Biological Chemistry, Vol. 275, No. 2, 14.01.2000, p. 1065-1072.

Research output: Contribution to journalArticle

Yang, Xiangli ; Ji, Xiaohui ; Shi, Xing Ming ; Cao, Xu. / Smad1 domains interacting with Hoxc-8 induce osteoblast differentiation. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 2. pp. 1065-1072.
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