Distinct transcriptional profiles characterize bone microenvironment mesenchymal cells rather than osteoblasts in relationship with multiple myeloma bone disease.
OBJECTIVE
Multiple myeloma (MM) is characterized by a high incidence of osteolytic bone lesions, which have been previously correlated with the gene expression profiles of MM cells. The aim of this study was to investigate the transcriptional patterns of cells in the bone microenvironment and their relationships with the presence of osteolysis in MM patients.


METHODS
Both mesenchymal (MSC) and osteoblastic (OB) cells were isolated directly from bone biopsies of MM patients and controls to perform gene expression profiling by microarrays and real-time polymerase chain reaction on selected bone-related genes.


RESULTS
We identified a series of upregulated and downregulated genes that were differentially expressed in the MSC cells of osteolytic and nonosteolytic patients. Comparison of the osteolytic and nonosteolytic samples also showed that the MSC cells and OB had distinct transcriptional patterns. No significantly modulated genes were found in the OBs of the osteolytic and nonosteolytic patients.


CONCLUSIONS
Our data suggest that the gene expression profiles of cells of the bone microenvironment are different in MM patients and controls, and that MSC cells, but not OBs, have a distinct transcriptional pattern associated with the occurrence of bone lesions in MM patients. These data support the idea that alterations in MSC cells may be involved in MM bone disease.
Todoerti
Katia
K
Dipartimento di Scienze Mediche, Università di Milano e U.O. Ematologia 1, Fondazione IRCCS Policlinico, Milan, Italy.
Lisignoli
Gina
G
Storti
Paola
P
Agnelli
Luca
L
Novara
Francesca
F
Manferdini
Cristina
C
Codeluppi
Katia
K
Colla
Simona
S
Crugnola
Monica
M
Abeltino
Manuela
M
Bolzoni
Marina
M
Sgobba
Valentina
V
Facchini
Andrea
A
Lambertenghi-Deliliers
Giorgio
G
Zuffardi
Orsetta
O
Rizzoli
Vittorio
V
Neri
Antonino
A
Giuliani
Nicola
N
D016723:Bone Remodeling / Q000235:genetics; D001842:Bone and Bones / Q000473:pathology*; D002455:Cell Division; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D009101:Multiple Myeloma / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D010014:Osteolysis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger