Osteoclasts secrete the chemotactic cytokine mim-1.
Osteoclasts are terminally differentiated, multinucleated cells of monocytic origin. In this study, we report that osteoclasts secrete a 35 kD protein and that phorbol myristate acetate treatment stimulates secretion dramatically. Peptide digests of the protein were analyzed by mass spectroscopy. The protein was identified as myb induced myeloid protein-1 precursor (mim-1 protein). Mim-1 is expressed specifically by hematopoietic cells and has no known function. It is homologous with the neutrophil chemokine, chondromodulin II, which stimulates proliferation of osteoblasts and chondrocytes. Western analysis showed that osteoclasts secrete mim-1 into culture media. Immunofluorescence studies demonstrated a cytoplasmic and perinuclear distribution of mim-1 in both avian osteoclasts and human osteoclast-like cells. Expression and secretion of a chemokine-like protein by osteoclasts suggests a novel signaling pathway in the bone microenvironment that may be involved in coordinating bone remodeling.
Falany
M L
ML
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Thames
A M
AM
McDonald
J M
JM
Blair
H C
HC
McKenna
M A
MA
Moore
R E
RE
Young
M K
MK
Williams
J P
JP
D000123:Acetyltransferases; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001862:Bone Resorption; D002273:Carcinogens; D002454:Cell Differentiation; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens; D019902:Chondrocytes / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D006133:Growth Substances / Q000737:chemistry; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism*; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors
D002273:Carcinogens; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; C103468:LECT2 protein, human; D011506:Proteins; D000123:Acetyltransferases; C077509:mim-1 protein, Gallus gallus; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate