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Osteoclast precursors do not express CD 68: results from CD 68 promoter‐driven RANK transgenic mice
Author(s) -
Jackson Melissa F.,
Scatena Marta,
Giachelli Cecilia M.
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12588
Subject(s) - osteoclast , myeloid , bone marrow , spleen , microbiology and biotechnology , mapk/erk pathway , biology , chemistry , phosphorylation , cancer research , immunology , receptor , biochemistry
Macrophages and osteoclasts are thought to derive from CD 68 lineage marker‐positive common myeloid precursors. We used the CD 68 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 FK 506 binding domain, which selectively binds the chemical inducer of dimerization AP 20187 and initiates signaling. iRANK mRNA was expressed in macrophages isolated from peritoneal cavity, spleen‐, and bone marrow‐derived myeloid cells. Unexpectedly, AP 20187 did not induce osteoclast formation in spleen‐ and bone marrow‐derived myeloid cells. However, AP 20187‐dependent RANK signaling induced ERK 1/2 phosphorylation and mRNA expression of MMP 9 and CathepsinK in peritoneal macrophages. Importantly, CD 68 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.