Involvement of human endogenous retroviral syncytin-1 in human osteoclast fusion.
Generation of osteoclasts through fusion of mono-nucleated precursors is a key event of bone physiology and bone resorption is inefficient without osteoclast fusion. Several factors playing a critical role in the fusion process have already been recognized, but the factors involved in the actual fusion of the lipid bilayers of their cell membranes are still unknown. Syncytin-1 is a protein encoded by a human endogenous retroviral gene which was stably integrated into the human ancestor genome more than 24 million years ago. Upon activation, syncytin-1 is able to destabilize the lipid bilayer of the target cell and to force the merging of plasma membranes. This protein is a key player in the fusion of cytotrophoblasts. In the present study, syncytin-1 as well as its putative receptor ASCT2 was found to be expressed in differentiating osteoclasts in vitro, both on mRNA and protein level. This was documented through Q-PCR, Western blot and immunofluorescence analyses. These in vitro findings were confirmed by immunohistochemical stainings in human iliac crest biopsies. A syncytin-1 inhibitory peptide reduced the number of nuclei per osteoclast by 30%, as well as TRACP activity. From a mechanistic point of view, it is interesting that the distribution of syncytin-1 immunoreactivity on the cell surface parallels that of actin, another important player in cell fusion, and that cell-cell proximity induces particular patterns of distribution of syncytin-1 and actin in the respective cells. These complementary observations support a critical role of syncytin-1 in osteoclast fusion, which is of special interest in view of its well-known ability to force the merging of plasma membranes.
Department of Clinical Cell Biology, Vejle Hospital, IRS/CSFU, University of Southern Denmark, Kabbeltoft 25, 7100 Vejle, Denmark. kent.soee@slb.regionsyddanmark.dk
Kent
K
Søe
Thomas L
TL
Andersen
Anne-Sofie
AS
Hobolt-Pedersen
Bolette
B
Bjerregaard
Lars-Inge
LI
Larsson
Jean-Marie
JM
Delaissé
D000595:Amino Acid Sequence; D015153:Blotting, Western; D002459:Cell Fusion; D002478:Cells, Cultured; D020077:Endogenous Retroviruses / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D015686:Gene Products, env / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D010010:Osteoclasts / Q000166:cytology*; D016133:Polymerase Chain Reaction; D011257:Pregnancy Proteins / Q000737:chemistry / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
D015686:Gene Products, env; D011257:Pregnancy Proteins; C405335:syncytin