|
Identification of Alternatively Spliced Forms of
human OSCAR in Osteoclasts |
김낙성,박호용,김현동 |
전남의대 |
|
Abstract |
Objective s: 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. |
Key Words:
Alternative splicing, Differentiation, OSCAR, Osteoclast |
|