A novel osteoblast-derived C-type lectin that inhibits osteoclast formation

We have cloned and expressed murine osteoclast inhibitory lectin (mOCIL), a 207-amino acid type II transmembrane C-type lectin. In osteoclast formatio n assays of primary murine calvarial osteoblasts with bone marrow cells, an tisense oligonucleotides for mOCIL increased tartrate-resistant acid phosph atase-positive mononucleate cell formation by 3-5-fold, whereas control oli gonucleotides had no effect. The extracellular domain of mOCIL, expressed a s a recombinant protein in Escherichia coli, dose-dependently inhibited mul tinucleate osteoclast formation in murine osteoblast and spleen cell co-cul tures as well as in spleen cell cultures treated with RANKL and macrophage colony-stimulating factor. Furthermore, mOCIL acted directly on macrophage/ monocyte cells as evidenced by its inhibitory action on adherent spleen cel l cultures, which were depleted of stromal and lymphocytic cells. mOCIL com pletely inhibited osteoclast formation during the proliferative phase of os teoclast formation and resulted in 70% inhibition during the differentiatio n phase. Osteoblast OCIL mRNA expression was enhanced by parathyroid hormon e, calcitriol, interleukin-1 alpha and -11, and retinoic acid. In rodent ti ssues, Northern blotting, in situ hybridization, and immunohistochemistry d emonstrated OCIL expression in osteoblasts and chondrocytes as well as in a variety of extraskeletal tissues. The overlapping tissue distribution of O CIL mRNA and protein with that of RANKL strongly suggests an interaction be tween these molecules in the skeleton and in extraskeletal tissues.