Distinct transcriptional profiles characterize bone microenvironment mesenchymal cells rather than osteoblasts in relationship with multiple myeloma bone disease

被引:63
作者
Todoerti, Katia [1 ,2 ]
Lisignoli, Gina [3 ]
Storti, Paola [4 ]
Agnelli, Luca [1 ,2 ]
Novara, Francesca [5 ]
Manferdini, Cristina [3 ]
Codeluppi, Katia [3 ]
Colla, Simona [4 ]
Crugnola, Monica [4 ]
Abeltino, Manuela [4 ]
Bolzoni, Marina [4 ]
Sgobba, Valentina [4 ]
Facchini, Andrea [3 ]
Lambertenghi-Deliliers, Giorgio [1 ,2 ]
Zuffardi, Orsetta [5 ]
Rizzoli, Vittorio [4 ]
Neri, Antonino [1 ,2 ]
Giuliani, Nicola [4 ]
机构
[1] Univ Milan, Dipartimento Sci Med, Milan, Italy
[2] Fdn IRCCS Policlin, UO Ematol 1, Milan, Italy
[3] Ist Ortoped Rizzoli, Lab Immunol & Genet, Bologna, Italy
[4] Azienda Osped Univ, Dipartimento Med Interna & Sci Biomed, Ematol & Ctr Trapianti Midollo Osseo, Parma, Italy
[5] Univ Pavia, Dipartimento Patol Umana & Ereditaria, Sez Biol Gen & Genet Med, I-27100 Pavia, Italy
关键词
STEM-CELLS; STROMAL CELLS; MARROW MICROENVIRONMENT; OSTEOLYTIC LESIONS; RANKL EXPRESSION; TRABECULAR BONE; GENE; PATHOPHYSIOLOGY; DIFFERENTIATION; PATHOGENESIS;
D O I
10.1016/j.exphem.2009.11.009
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
引用
收藏
页码:141 / 153
页数:13
相关论文
共 55 条
[1]   Molecular classification of multiple myeloma:: A distinct transcriptional profile characterizes patients expressing CCND1 and negative for 14q32 translocations [J].
Agnelli, L ;
Bicciato, S ;
Mattioli, M ;
Fabris, S ;
Intini, D ;
Verdelli, D ;
Baldini, L ;
Morabito, F ;
Callea, V ;
Lombardi, L ;
Neri, A .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (29) :7296-7306
[2]   The WWOX tumor suppressor is essential for postnatal survival and normal bone metabolism [J].
Aqeilan, Rami I. ;
Hassan, Mohammad Q. ;
de Bruin, Alain ;
Hagan, John P. ;
Volinia, Stefano ;
Palumbo, Titziana ;
Hussain, Sadiq ;
Lee, Suk-Hee ;
Gaur, Tripti ;
Stein, Gary S. ;
Lian, Jane B. ;
Croce, Carlo M. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (31) :21629-21639
[3]   Phenotypic and functional characterization of bone marrow mesenchymal stem cells derived from patients with multiple myeloma [J].
Arnulf, B. ;
Lecourt, S. ;
Soulier, J. ;
Ternaux, B. ;
Lacassagne, M-Noelle ;
Crinquette, A. ;
Dessoly, J. ;
Sciaini, A-K ;
Benbunan, M. ;
Chomienne, C. ;
Fermand, J-P ;
Marolleau, J-P ;
Larghero, J. .
LEUKEMIA, 2007, 21 (01) :158-163
[4]   RANKL expression is related to the differentiation state of human osteoblasts [J].
Atkins, GJ ;
Kostakis, P ;
Pan, BQ ;
Farrugia, A ;
Gronthos, S ;
Evdokiou, A ;
Harrison, K ;
Findlay, DM ;
Zannettino, ACW .
JOURNAL OF BONE AND MINERAL RESEARCH, 2003, 18 (06) :1088-1098
[5]   MECHANISMS OF BONE DESTRUCTION IN MULTIPLE-MYELOMA - THE IMPORTANCE OF AN UNBALANCED PROCESS IN DETERMINING THE SEVERITY OF LYTIC BONE-DISEASE [J].
BATAILLE, R ;
CHAPPARD, D ;
MARCELLI, C ;
DESSAUW, P ;
SANY, J ;
BALDET, P ;
ALEXANDRE, C .
JOURNAL OF CLINICAL ONCOLOGY, 1989, 7 (12) :1909-1914
[6]   RECRUITMENT OF NEW OSTEOBLASTS AND OSTEOCLASTS IS THE EARLIEST CRITICAL EVENT IN THE PATHOGENESIS OF HUMAN MULTIPLE-MYELOMA [J].
BATAILLE, R ;
CHAPPARD, D ;
MARCELLI, C ;
DESSAUW, P ;
BALDET, P ;
SANY, J ;
ALEXANDRE, C .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 88 (01) :62-66
[7]   HOX gene analysis of endothelial cell differentiation in human bone marrow-derived mesenchymal stem cells [J].
Chung, Namhyun ;
Jee, Bo Keun ;
Chae, Song Wha ;
Jeon, Yang-Whan ;
Lee, Kweon Haeng ;
Rha, Hyoung Kyun .
MOLECULAR BIOLOGY REPORTS, 2009, 36 (02) :227-235
[8]   Bone marrow mesenchymal stem cells are abnormal in multiple myeloma [J].
Corre, J. ;
Mahtouk, K. ;
Attal, M. ;
Gadelorge, M. ;
Huynh, A. ;
Fleury-Cappellesso, S. ;
Danho, C. ;
Laharrague, P. ;
Klein, B. ;
Reme, T. ;
Bourin, P. .
LEUKEMIA, 2007, 21 (05) :1079-1088
[9]   The pathogenesis of the bone disease of multiple myeloma [J].
Edwards, Claire M. ;
Zhuang, Junling ;
Mundy, Gregory R. .
BONE, 2008, 42 (06) :1007-1013
[10]   Increasing Wnt signaling in the bone marrow microenvironment inhibits the development of myeloma bone disease and reduces tumor burden in bone in vivo [J].
Edwards, Claire M. ;
Edwards, James R. ;
Lwin, Seint T. ;
Esparza, Javier ;
Oyajobi, Babatunde O. ;
McCluskey, Brandon ;
Munoz, Steven ;
Grubbs, Barry ;
Mundy, Gregory R. .
BLOOD, 2008, 111 (05) :2833-2842