An assessment of ADAMs in bone cells: absence of TACE activity prevents osteoclast recruitment and the formation of the marrow cavity in developing long bones.
ADAMs (A Disintegrin And Metalloprotease domain) are metalloprotease-disintegrin proteins that have been implicated in cell adhesion, protein ectodomain shedding, matrix protein degradation and cell fusion. Since such events are critical for bone resorption and osteoclast recruitment, we investigated whether they require ADAMs. We report here which ADAMs we have identified in bone cells, as well as our analysis of the generation, migration and resorptive activity of osteoclasts in developing metatarsals of mouse embryos lacking catalytically active ADAM 17 [TNFalpha converting enzyme (TACE)]. The absence of TACE activity still allowed the generation of cells showing an osteoclastic phenotype, but prevented their migration into the core of the diaphysis and the subsequent formation of marrow cavity. This suggests a role of TACE in the recruitment of osteoclasts to future resorption sites.
Boissy
Patrice
P
Nordic Bioscience/CCBR, Herlev Hovedgade 207, 2730 Herlev, Denmark. patboi@vs.vejleamt.dk
Lenhard
Thomas R
TR
Kirkegaard
Tove
T
Peschon
Jacques J
JJ
Black
Roy A
RA
Delaissé
Jean-Marie
JM
del Carmen Ovejero
Maria
M
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000818:Animals; D001846:Bone Development / Q000502:physiology*; D001853:Bone Marrow / Q000201:enzymology / Q000378:metabolism*; D001862:Bone Resorption / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D018483:Diaphyses / Q000166:cytology / Q000254:growth & development; D019483:Disintegrins / Q000737:chemistry; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008682:Metatarsal Bones / Q000254:growth & development / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D010010:Osteoclasts / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D010641:Phenotype; D017434:Protein Structure, Tertiary; D053245:RANK Ligand; D011817:Rabbits; D053246:Receptor Activator of Nuclear Factor-kappa B; D014409:Tumor Necrosis Factor-alpha
D002352:Carrier Proteins; D017931:DNA Primers; D019483:Disintegrins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606463:Adam17 protein, mouse