ISSN:
1432-0827
Keywords:
Key words: Meltrin — Fusion — Macrophages — Osteoclasts — Osteoblasts.
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Medicine
,
Physics
Notes:
Abstract. The formation of multinucleated cells such as myotubes, macrophage-derived giant cells (MGC), and osteoclasts is the result of cell-cell fusion of mononuclear precursors. Meltrin-α, -β, and -γ are members of a recently discovered family of proteins that contain disintegrin and metalloprotease domains and are related to fertilin, a protein involved in egg-sperm fusion. Based on this and evidence implicating meltrin-α in myoblast formation, we have investigated the possibility that meltrins may also play a role in the formation of MGC and osteoclasts. Using in situ RT-PCR, we have determined that murine mononuclear alveolar macrophages cultured under basal conditions express the transcript for meltrin-β, but not for meltrin-α. However, meltrin-α mRNA appeared in mononuclear cells before cell fusion after treatment with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], a potent inducer of giant cell and osteoclast formation. Moreover, addition of meltrin-α antisense oligonucleotides to the cultures caused a 50% inhibition of giant cell formation. Similarly, meltrin-α antisense oligonucleotides inhibited by 70% the formation of multinucleated osteoclast-like cells expressing tartrate-resistant acid phosphatase (TRAP) in co-cultures of bone marrow cells and osteoblastic cells (2107) in the presence of 1,25(OH)2D3. Mononucleated TRAP-positive cells, induced by 1,25(OH)2D3 in the co-cultures, also expressed meltrin-α mRNA, but their number was not changed in the presence of meltrin-α antisense oligonucleotide. In contrast to mononuclear macrophages and osteoclast-like cells, murine bone marrow stroma and calvaria derived-cell lines (+/+ LDA.11 and 2107), primary cultures of calvaria cells, and primary cultures of bone marrow cells expressed both meltrin-α and -β mRNA under basal conditions; whereas embryonic fibroblasts (NIH3T3) expressed only the meltrin-β transcript. Upregulation of meltrin-α protein expression during cell fusion in alveolar macrophages and expression in osteoblastic cell lines were confirmed by Western blot analysis. These observations demonstrate that meltrins play a role in MGC and osteoclast formation from mononuclear precursors, as in the case with myotubes.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002239900641
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