βig-h3 mediates osteoblast adhesion and inhibits differentiation

Narendra Thapa, Kae Bok Kang, In-San Kim

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

βig-h3 is an extracellular matrix (ECM) protein induced by TGF-β, and it has motifs interacting with the α3β1, αvβ5, and αvβ3 integrins. Our previous study shows the role of βig-h3 in osteoblast differentiation and its involvement in melorheostosis, a rare bone disease. Here we demonstrate that βig-h3 expression is down-regulated during the early stage of differentiation of the murine preosteoblastic cell line, KS483. The recombinant βig-h3 and its FAS1 domain significantly inhibited in vitro osteoblast differentiation as evaluated by matrix mineralization/bone nodule formation. Furthermore, inhibition of expression of osteoblast differentiation marker genes [such as type I collagen, alkaline phosphatase, and osteocalcin (OC)] was accompanied by suppression of osteoblast-specific transcription factors, Cbfa1/Runx2 and osterix. Flow cytometric analyses, cell adhesion, and inhibition assays disclosed αvβ3 and αvβ5 as the principal integrins mediating the adhesion of osteoblastic cells to βig-h3. The disruption of interactions between βig-h3 and osteoblasts by a function-blocking antibody specific for αvβ3 but not for αvβ5 abolished the inhibitory effect of βig-h3 on osteoblast differentiation. We suggest that these interacting integrins may play an important role in βig-h3-mediated inhibition of osteoblast differentiation.

Original languageEnglish
Pages (from-to)232-242
Number of pages11
JournalBone
Volume36
Issue number2
DOIs
Publication statusPublished - 2005 Jan 1
Externally publishedYes

Fingerprint

Osteoblasts
Integrins
Cell Adhesion
Melorheostosis
Blocking Antibodies
Extracellular Matrix Proteins
Bone Diseases
Osteocalcin
Differentiation Antigens
Rare Diseases
Collagen Type I
Osteogenesis
Alkaline Phosphatase
Transcription Factors
Cell Line
Genes

Keywords

  • Bone formation
  • Osteoblast differentiation
  • TGF-β
  • αvβ3/β5 integrin
  • βig-h3

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

βig-h3 mediates osteoblast adhesion and inhibits differentiation. / Thapa, Narendra; Kang, Kae Bok; Kim, In-San.

In: Bone, Vol. 36, No. 2, 01.01.2005, p. 232-242.

Research output: Contribution to journalArticle

Thapa, Narendra ; Kang, Kae Bok ; Kim, In-San. / βig-h3 mediates osteoblast adhesion and inhibits differentiation. In: Bone. 2005 ; Vol. 36, No. 2. pp. 232-242.
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