Another recent report found that dynamin and endocytotic processes were required for fusion of both pre-osteoclasts and myoblasts. Besides these factors, which are mostly ubiquitously, or at least widely, expressed, two related transmembrane proteins, which are known to be essential for pre-osteoclast fusion, are restricted to pre-osteoclasts and pre-foreign body giant cells: dendritic cell-specific transmembrane protein and osteoclast-stimulatory transmembrane protein. Neither protein has homology to the other fusion factors described above. The ��STAMPs�� are both very strongly induced during stimulation of osteoclast differentiation by RANKL or FBGC by GM-CSF, and their expression has only been detected in monocyte/macrophage lineage cells. Both are predicted to be multiple-pass transmembrane proteins with little direct amino acid homology to each other, but with strong similarity in predicted secondary structure. Transmembrane topology prediction algorithms yield several models for intra and extracellular orientation and for the number of transmembrane domains for both OC- and DC-STAMP. Although some Idebenone analyses have predicted a 7-pass transmembrane structure for DC-STAMP, the most frequent prediction for DC and OC-STAMP is 6transmembranedomains with both the N-and C-termini residing in the cytoplasm. Interestingly, studies of cells from homozygous knockout mice found that each of the STAMPs is required on only one cell undergoing fusion, showing that they cannot be forming ��fusion bridges�� to themselves Saxagliptin across the cell-cell junction. Mononuclear osteoclasts from each knock out strain were shown in pit forming assays to be highly deficient in bone resorption capacity. Dcstamp-/- cells resorbed about 3-fold less area than wild-type cells, and Ocstamp-/- cells resorbed about 6-foldless. Consistent with this, the DC-STAMP KO mice also had a roughly 3-fold increase in trabecular bone in the metaphysis compared to WT animals. Unexpectedly, however, the OC-STAMP KO mice were reported to have no changes in skeletal parameters despite the loss of pit-forming ability.
Neither protein has homology to the other fusion factors described above
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