Cloning and identification of human stem cell antigen as a novel inhibitor of osteoclast formation and bone resorption

S. J. Choi, R. Davlin, S. V. Baddy, G. David Roodman

Research output: Contribution to journalArticle

Abstract

Increased osteoclast activity is responsible for the enhanced bone destruction in postmenopausal osteoporosis, Paget's disease, bone metastasis and hypercalcémie of malignancy. However, the number of known inhibitory factors that block osteoclast formation and bone résorption are limited. Therefore, we used an expression cloning approach to identify novel factors produced by osteoclasts that inhibit osteoclast activity. A candidate clone was identified and isolated from a human osteoclast-like muhtinucleated cell (MNC) cDNA library, named osteoclast inhibitory peptide-1 IOIP-1), and the cDNA sequence was determined. This sequence matched that of the recently identified human stem cell antigen (hSca), was structurally similar to the mouse Ly-6 gene family, and the sequence predicted it was a GPI-anchored protein that had a cleavable C-terminal peptide. Western blot analysis of conditioned media from 293 cells transfected with the OIP-1 cDNA clone confirmed that OIP-1 was released into the media as a glycosylated membrane-bound GPI-linked protein. Interestingly, both recombinant OIP-1 expressed in E. coll, which does not have GPI linker, and mammalian cell expressed OIP-1 significantly reduced osteoclast-like MNC formation induced by 1,25-(OH)2D3 or PTHrP in mouse and human bone marrow cultures, and inhibited 45Ca release from prelabeled bone in fetal rat organ cultures. In contrast, rOIP-1 did not inhibit the growth of a variety of other cell types. These data indicate that hSca is a novel, relatively specific inhibitor of osteoclast formation and bone résorption.

Original languageEnglish (US)
Pages (from-to)729
Number of pages1
JournalExperimental Hematology
Volume26
Issue number8
StatePublished - 1998
Externally publishedYes

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Forensic Anthropology
Osteoclasts
Bone Resorption
Organism Cloning
Stem Cells
Antigens
Osteogenesis
GPI-Linked Proteins
Complementary DNA
Clone Cells
Osteitis Deformans
Parathyroid Hormone-Related Protein
Bone and Bones
Peptides
Postmenopausal Osteoporosis
Organ Culture Techniques
Conditioned Culture Medium
Gene Library
Bone Marrow
Western Blotting

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Cloning and identification of human stem cell antigen as a novel inhibitor of osteoclast formation and bone resorption. / Choi, S. J.; Davlin, R.; Baddy, S. V.; Roodman, G. David.

In: Experimental Hematology, Vol. 26, No. 8, 1998, p. 729.

Research output: Contribution to journalArticle

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