Cloning and identification of human Sca as a novel inhibitor of osteoclast formation and bone resorption

Autor: Rowena D. Devlin, Sakamuri V. Reddy, Sun Jin Choi, G. D. Roodman, Cheikh Menaa, Hoyeon Chung
Jazyk: angličtina
Rok vydání: 1998
Předmět:
musculoskeletal diseases
Proteasome Endopeptidase Complex
Stromal cell
Molecular Sequence Data
Clone (cell biology)
Osteoclasts
Bone Marrow Cells
Biology
Transfection
Bone resorption
Cell Line
Mice
Calcitriol
Osteoclast
Complementary DNA
medicine
Escherichia coli
Animals
Antigens
Ly
Humans
Amino Acid Sequence
Bone Resorption
Cloning
Molecular
Cells
Cultured
Adaptor Proteins
Signal Transducing
Mice
Inbred BALB C
Base Sequence
cDNA library
Parathyroid Hormone-Related Protein
Bone metastasis
Membrane Proteins
Proteins
General Medicine
LIM Domain Proteins
medicine.disease
Molecular biology
Recombinant Proteins
Rats
medicine.anatomical_structure
Cell culture
Culture Media
Conditioned
Protein Biosynthesis
ATPases Associated with Diverse Cellular Activities
Calcium
Stromal Cells
Research Article
Transcription Factors
Popis: Increased osteoclast activity is responsible for the enhanced bone destruction in postmenopausal osteoporosis, Paget's disease, bone metastasis, and hypercalcemia of malignancy. However, the number of known inhibitory factors that block osteoclast formation and bone resorption 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 multinucleated cell (MNC) cDNA library, named osteoclast inhibitory peptide-1 (OIP-1), and the cDNA sequence was determined. This sequence matched that of the recently identified human stem cell antigen, was structurally similar to the mouse Ly-6 gene family, and the sequence predicted it was a glycosyl phosphatidyl inositol (GPI)-anchored protein that had a cleavable COOH-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 membrane-bound GPI-linked protein. Interestingly, both recombinant OIP-1 expressed in Escherichia coli (which does not have GPI linker) and OIP-1 expressed by mammalian cells significantly reduced osteoclast-like MNC formation induced by 1,25-dihydroxyvitamin D3 or PTH-related protein in mouse and human bone marrow cultures, and inhibited 45Ca release from prelabeled bone in fetal rat organ cultures. In contrast, recombinant OIP-1 did not inhibit the growth of a variety of other cell types. These data indicate that OIP-1 is a novel, specific inhibitor of osteoclast formation and bone resorption.
Databáze: OpenAIRE
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