Identification of Alternatively Spliced Forms of human OSCAR in Osteoclasts.
10.11005/kjbm.2012.19.1.11
- Author:
Nacksung KIM
1
;
Hong Yong PARK
;
Hyun Dong KIM
Author Information
1. Department of Pharmacology, Chonnam National University Medical School, Gwangju, Korea. nacksung@chonnam.ac.kr
- Publication Type:Original Article
- Keywords:
Alternative splicing;
Differentiation;
OSCAR;
Osteoclast
- MeSH:
Acid Phosphatase;
Alternative Splicing;
Blotting, Western;
Clone Cells;
DNA;
Flow Cytometry;
Giant Cells;
Humans;
Isoenzymes;
Macrophage Colony-Stimulating Factor;
Osteoclasts;
Protein Isoforms;
RANK Ligand;
RNA
- From:Korean Journal of Bone Metabolism
2012;19(1):11-20
- CountryRepublic of Korea
- Language:English
-
Abstract:
OBJECTIVES: Osteoclasts are multinucleated giant cells which can resorb bone and differentiated from hematopoietic cells. We have previously reported murine osteoclast-associated receptor (OSCAR) may be an important bone-specific regulator of osteoclast differentiation. We have cloned soluble form of human OSCAR (hOSCAR) and examined the role of hOSCAR on osteoclast differentiation. METHODS: Osteoclast differentiation was induced by treatment with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP) staining and pit formation were performed. Expression was measured by flow cytometry analysis, Northern and Western blot analysis. RESULTS: hOSCAR is expressed in osteoclast cells and involved in the differentiation of osteoclasts from peripheral blood mononuclear cells (PBMC). Two alternatively spliced forms (soluble hOSCAR [hOSCAR-S]) of hOSCAR were identified from osteoclasts complementary deoxyribonucleic acid (cDNA) library derived from PBMC. Putative transmembrane domain was not found in hOSCAR-S forms and it suggested that these forms might be secreted from osteoclast cells. These secreted forms of hOSCAR attenuated RANKL-induced osteoclast formation and bone resorption. CONCLUSIONS: Human osteoclasts express at least five different OSCAR messenger ribonucleic acid (mRNA) isoforms which could play different regulatory roles for differentiation. The secreted forms of hOSCAR might be a negative regulator of membrane-bounded forms of OSCAR.
