Distinct transcriptional profiles characterize bone microenvironment mesenchymal cells rather than osteoblasts in relationship with multiple myeloma bone disease
Received 18 August 2009; received in revised form 5 November 2009; accepted 24 November 2009. published online 07 December 2009.
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.
Materials and 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.
aDipartimento di Scienze Mediche, Università di Milano e U.O. Ematologia 1, Fondazione IRCCS Policlinico, Milan, Italy
bLaboratorio di Immunologia e Genetica, Istituti Ortopedici Rizzoli, Bologna, Italy
cEmatologia e Centro Trapianti Midollo Osseo, Dipartimento di Medicina Interna e Scienze Biomediche, Azienda Ospedaliero-Universitaria, Parma, Italy
dDipartimento di Patologia Umana ed Ereditaria, Sezione Biologia generale e Genetica Medica, University of Pavia, Pavia, Italy
Offprint requests to: Nicola Giuliani, M.D., Ph.D., Department of Internal Medicine and Biomedical Science, University of Parma, Via Gramsci 14, Parma 43100, Italy
ABSTRACT