A Novel Osteoblast-derived C-type Lectin That Inhibits Osteoclast Formation

• Published in: The Journal of biological chemistry 2001-05, Vol.276 (18), p.14916-14923
• Main Authors: Zhou, Hong, Kartsogiannis, Vicky, Hu, Yun Shan, Elliott, Jan, Quinn, Julian M.W., McKinstry, William J., Gillespie, Matthew T., Ng, Kong Wah
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Bone Marrow Cells - metabolism; Cell Division - drug effects; DNA, Complementary; Humans; Immunohistochemistry; In Situ Hybridization; Lectins - chemistry; Lectins - genetics; Lectins - pharmacology; Lectins, C-Type; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - pharmacology; Mice; Molecular Sequence Data; Osteoblasts - metabolism; Osteoclasts - drug effects; Rats; Recombinant Proteins - pharmacology; RNA, Messenger - genetics; Sequence Homology, Amino Acid
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M011554200

We have cloned and expressed murineosteoclast inhibitorylectin (mOCIL), a 207-amino acid type II transmembrane C-type lectin. In osteoclast formation assays of primary murine calvarial osteoblasts with bone marrow cells, antisense oligonucleotides for mOCIL increased tartrate-resistant acid phosphatase-positive mononucleate cell formation by 3–5-fold, whereas control oligonucleotides had no effect. The extracellular domain of mOCIL, expressed as a recombinant protein inEscherichia coli, dose-dependently inhibited multinucleate osteoclast formation in murine osteoblast and spleen cell co-cultures 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 cell cultures, which were depleted of stromal and lymphocytic cells. mOCIL completely inhibited osteoclast formation during the proliferative phase of osteoclast formation and resulted in 70% inhibition during the differentiation phase. Osteoblast OCIL mRNA expression was enhanced by parathyroid hormone, calcitriol, interleukin-1α and -11, and retinoic acid. In rodent tissues, Northern blotting, in situ hybridization, and immunohistochemistry demonstrated OCIL expression in osteoblasts and chondrocytes as well as in a variety of extraskeletal tissues. The overlapping tissue distribution of OCIL mRNA and protein with that of RANKL strongly suggests an interaction between these molecules in the skeleton and in extraskeletal tissues.AF321553