Soluble decoy receptor 3 modulates the survival and formation of osteoclasts from multiple myeloma bone disease patients.
Decoy receptor 3 (DcR3), a member of the tumor necrosis factor (TNF) receptor superfamily, is known to be involved in cell survival and osteoclast (OC) formation. In this study, we show that malignant plasma cells and T lymphocytes from multiple myeloma (MM) bone disease patients, as well as Karpas 909, a human myeloma cell line, directly produce DcR3. By interacting with FasL, this molecule could inhibit OC apoptosis. In fact, the use of a neutralizing anti-DcR3 antibody induces a reduction of cell viability with a consequent increase of apoptotic cell number, the activation of caspase-8 and -3, and DNA fragmentation. Furthermore, we show that DcR3 supports OC formation in samples from MM patients through the upregulation of RANKL and TNFalpha by T lymphocytes and only TNFalpha by CD14+ cells. In conclusion, our data provide the first evidence of the expression of DcR3 in MM, and the involvement of this molecule in supporting the survival and formation of OCs from MM bone disease patients. The production of DcR3 by T lymphocytes confers these cells a role in the pathogenesis of bone disease associated with MM.
Colucci
S
S
Department of Human Anatomy and Histology, University of Bari, Bari, Italy.
Brunetti
G
G
Mori
G
G
Oranger
A
A
Centonze
M
M
Mori
C
C
Cantatore
F P
FP
Tamma
R
R
Rizzi
R
R
Liso
V
V
Zallone
A
A
Grano
M
M
D000368:Aged; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology*; D010014:Osteolysis / Q000378:metabolism / Q000473:pathology*; D010950:Plasma Cells / Q000166:cytology / Q000502:physiology; D053245:RANK Ligand / Q000378:metabolism; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D053245:RANK Ligand; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8