ADAM8: A novel osteoclast stimulating factor

Jin Choi Sun Jin Choi, J. H. Han, G. David Roodman

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

We used polymerase chain reaction (PCR)-selective complementary DNA (cDNA) subtraction hybridization with an immortalized murine osteoclast (OCL) precursor cell line to identify genes that are highly expressed in OCLs compared with OCL precursors and which may be involved in the OCL differentiation process. ADAM8 was one of the 50 genes identified. ADAM (a disintegrin and metalloproteinase) peptides are membrane-bound proteins that can act as cell-to-cell and cell-to-matrix adhesion molecules, degrade the extracellular matrix, and play a role in tissue morphogenesis. Addition of antisense (AS) S-oligonucleotides for ADAM8 (1-10 nM) to mouse bone marrow cultures treated with 10-9 M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] significantly inhibited OCL formation compared with treatment with the control S-oligonucleotide. Furthermore, conditioned media from 293 cells transiently transfected with a secretable form of the ADAM8 cDNA increased OCL formation in a dose-dependent manner. In addition, treatment of OCLs with soluble ADAM8 conditioned media significantly increased pit formation per dentin slice compared with control OCLs. Time course studies indicated that ADAM8 increased OCL formation only when it was present during days 4-7 of the 7-day culture period. Structural analysis, using truncated constructs of ADAM8, showed that the cysteine-rich/disintegrin domain was responsible for its OCL stimulatory activity. Western blot analysis confirmed that the soluble form of ADAM8 is present in normal marrow cultures. These data suggest that ADAM8 plays an important role in OCL formation and acts primarily at the later stages of OCL differentiation.

Original languageEnglish (US)
Pages (from-to)814-822
Number of pages9
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume16
Issue number5
StatePublished - 2001
Externally publishedYes

Fingerprint

Osteoclasts
Disintegrins
Conditioned Culture Medium
Complementary DNA
Bone Marrow
Cell-Matrix Junctions
osteoclast stimulating factor
Calcitriol
Antisense Oligonucleotides
Metalloproteases
Dentin
Morphogenesis
Oligonucleotides
Genes
Extracellular Matrix
Cysteine
Membrane Proteins
Western Blotting
Cell Line
Polymerase Chain Reaction

Keywords

  • ADAM8
  • Macrophage colony-stimulating factor
  • Osteoclasts
  • Polymerase chain reaction

ASJC Scopus subject areas

  • Surgery

Cite this

ADAM8 : A novel osteoclast stimulating factor. / Sun Jin Choi, Jin Choi; Han, J. H.; Roodman, G. David.

In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Vol. 16, No. 5, 2001, p. 814-822.

Research output: Contribution to journalArticle

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