Osteoclasts secrete the chemotactic cytokine mim-1

Osteoclasts are terminally differentiated, multinucleated cells of monocyti c origin. In this study, we report that osteoclasts secrete a 35 kD protein and that phorbol myristate acetate treatment stimulates secretion dramatic ally. Peptide digests of the protein were analyzed by mass spectroscopy. Th e 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, chondromod ulin II, which stimulates proliferation of osteoblasts and chondrocytes. We stern analysis showed that osteoclasts secrete mim-1 into culture media. Im munofluorescence studies demonstrated an cytoplasmic and perinuclear distri bution of mim-1 in both avian osteoclasts and human osteoclast-like cells. Expression and secretion of a chemokine-like protein by osteoclasts suggest s a novel signaling pathway in the bone microenvironment that may be involv ed in coordinating bone remodeling. (C) 2001 Academic Press.