GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:11341326

From GONUTS
Jump to: navigation, search
Citation

Choi, SJ, Han, JH and Roodman, GD (2001) ADAM8: a novel osteoclast stimulating factor. J. Bone Miner. Res. 16:814-22

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.

Links

PubMed Online version:10.1359/jbmr.2001.16.5.814

Keywords

ADAM Proteins; Animals; Antigens, CD; Antigens, Surface/genetics; Antigens, Surface/physiology; Bone Marrow Cells/cytology; Bone Resorption/metabolism; Cell Differentiation; Cell Line; Cells, Cultured; Culture Media, Conditioned; Dentin/metabolism; Disintegrins/genetics; Disintegrins/physiology; Gene Expression; Humans; Leukocyte Count; Leukocytes, Mononuclear/cytology; Membrane Glycoproteins/genetics; Membrane Proteins/genetics; Metalloendopeptidases/genetics; Metalloendopeptidases/physiology; Mice; Oligonucleotides, Antisense; Osteoclasts/cytology; Osteoclasts/metabolism; Polymerase Chain Reaction/methods; Solubility; Stem Cells/cytology; Stem Cells/metabolism; Time Factors

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:ADAM8

involved_in

GO:0000902: cell morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ADAM8

involved_in

GO:0007160: cell-matrix adhesion

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ADAM8

involved_in

GO:0061025: membrane fusion

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ADAM8

involved_in

GO:0048729: tissue morphogenesis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ADAM8

involved_in

GO:0045780: positive regulation of bone resorption

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.