Osteoclast precursors do not express CD68: results from CD68 promoter‐driven RANK transgenic mice

• Published in: FEBS letters 2017-03, Vol.591 (5), p.728-736
• Main Authors: Jackson, Melissa F., Scatena, Marta, Giachelli, Cecilia M.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - genetics; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - genetics; Antigens, Differentiation, Myelomonocytic - metabolism; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Cathepsin K - genetics; Cathepsin K - metabolism; CD68; Cell Differentiation - drug effects; Gene Expression Regulation; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Mice; Mice, Transgenic; Mitogen-Activated Protein Kinase 1 - genetics; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - genetics; Mitogen-Activated Protein Kinase 3 - metabolism; Myeloid Cells - cytology; Myeloid Cells - drug effects; Myeloid Cells - metabolism; osteoclast precursors; Osteoclasts - cytology; Osteoclasts - drug effects; Osteoclasts - metabolism; Peritoneal Cavity - cytology; Promoter Regions, Genetic; RANK; Receptor Activator of Nuclear Factor-kappa B - genetics; Receptor Activator of Nuclear Factor-kappa B - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Signal Transduction; Spleen - cytology; Spleen - drug effects; Spleen - metabolism; Tacrolimus - analogs & derivatives; Tacrolimus - pharmacology; Tacrolimus Binding Proteins - genetics; Tacrolimus Binding Proteins - metabolism
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1002/1873-3468.12588

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.