Osteoclast precursors do not express CD68: results from CD68 promoter-driven RANK transgenic mice.
Macrophages and osteoclasts are thought to derive from CD68 lineage marker-positive common myeloid precursors. We used the CD68 promoter to drive an inducible receptor activator of NF-κB (iRANK) construct that selectively activates RANK signaling in myeloid cells in vivo. The cytoplasmic portion of RANK was fused to a mutant FK506 binding domain, which selectively binds the chemical inducer of dimerization AP20187 and initiates signaling. iRANK mRNA was expressed in macrophages isolated from peritoneal cavity, spleen-, and bone marrow-derived myeloid cells. Unexpectedly, AP20187 did not induce osteoclast formation in spleen- and bone marrow-derived myeloid cells. However, AP20187-dependent RANK signaling induced ERK1/2 phosphorylation and mRNA expression of MMP9 and CathepsinK in peritoneal macrophages. Importantly, CD68 was not expressed until day 3 and day 5 in bone marrow and spleen myeloid cells, respectively. Contrary to dogma, osteoclast precursors do not express the lineage marker CD68.
Department of Bioengineering, University of Washington, Seattle, WA, USA.
Melissa F
MF
Jackson
Department of Bioengineering, University of Washington, Seattle, WA, USA.
Marta
M
Scatena
Department of Bioengineering, University of Washington, Seattle, WA, USA.
Cecilia M
CM
Giachelli
D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D056657:Cathepsin K / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D005786:Gene Expression Regulation; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D011401:Promoter Regions, Genetic; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D056657:Cathepsin K; D020780:Matrix Metalloproteinase 9; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053246:Receptor Activator of Nuclear Factor-kappa B; D011993:Recombinant Fusion Proteins; D016559:Tacrolimus; D022021:Tacrolimus Binding Proteins; C463061:AP20187; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C505687:Tnfrsf11a protein, mouse; C535148:Mapk1 protein, mouse; C534132:Ctsk protein, mouse; C501830:Mmp9 protein, mouse

RANK
; CD68; osteoclast precursors