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Isolation of a Human Homolog of Osteoclast Inhibitory Lectin That Inhibits the Formation and Function of Osteoclasts
Author(s) -
Hu Yun Shan,
Zhou Hong,
Myers Damian,
Quinn Julian MW,
Atkins Gerald J,
Ly Chi,
Gange Christine,
Kartsogiannis Vicky,
Elliott Jan,
Kostakis Panagiota,
Zannettino Andrew CW,
Cromer Brett,
Mckinstry William J,
Findlay David M,
Gillespie Matthew T,
Ng Kong Wah
Publication year - 2004
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.0301215
Subject(s) - osteoclast , microbiology and biotechnology , biology , extracellular , recombinant dna , biochemistry , receptor , gene
Osteoclast inhibitory lectin (OCIL) is a newly recognized inhibitor of osteoclast formation. We identified a human homolog of OCIL and its gene, determined its regulation in human osteoblast cell lines, and established that it can inhibit murine and human osteoclast formation and resorption. OCIL shows promise as a new antiresorptive. Introduction: Murine and rat osteoclast inhibitory lectins (mOCIL and rOCIL, respectively) are type II membrane C‐type lectins expressed by osteoblasts and other extraskeletal tissues, with the extracellular domain of each, expressed as a recombinant protein, able to inhibit in vitro osteoclast formation. Materials and Methods: We isolated the human homolog of OCIL (hOCIL) from a human fetal cDNA library that predicts a 191 amino acid type II membrane protein, with the 112 amino acid C‐type lectin region in the extracellular domain having 53% identity with the C‐type lectin sequences of rOCIL and mOCIL. The extracellular domain of hOCIL was expressed as a soluble recombinant protein in E. coli , and its biological effects were determined. Results and Conclusions: The hOCIL gene is 25 kb in length, comprised of five exons, and is a member of a superfamily of natural killer (NK) cell receptors encoded by the NK gene complex located on chromosome 12. Human OCIL mRNA expression is upregulated by interleukin (IL)‐1α and prostaglandin E 2 (PGE 2 ) in a time‐dependent manner in human osteogenic sarcoma MG63 cells, but not by dexamethasone or 1,25 dihydroxyvitamin D 3 . Soluble recombinant hOCIL had biological effects comparable with recombinant mOCIL on human and murine osteoclastogenesis. In addition to its capacity to limit osteoclast formation, OCIL was also able to inhibit bone resorption by mature, giant‐cell tumor‐derived osteoclasts. Thus, a human homolog of OCIL exists that is highly conserved with mOCIL in its primary amino acid sequence (C‐lectin domain), genomic structure, and activity to inhibit osteoclastogenesis.