Experimental Hematology
Volume 38, Issue 2 , Pages 141-153, February 2010

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

  • Katia Todoerti

      Affiliations

    • Dipartimento di Scienze Mediche, Università di Milano e U.O. Ematologia 1, Fondazione IRCCS Policlinico, Milan, Italy
  • ,
  • Gina Lisignoli

      Affiliations

    • Laboratorio di Immunologia e Genetica, Istituti Ortopedici Rizzoli, Bologna, Italy
  • ,
  • Paola Storti

      Affiliations

    • Ematologia e Centro Trapianti Midollo Osseo, Dipartimento di Medicina Interna e Scienze Biomediche, Azienda Ospedaliero-Universitaria, Parma, Italy
  • ,
  • Luca Agnelli

      Affiliations

    • Dipartimento di Scienze Mediche, Università di Milano e U.O. Ematologia 1, Fondazione IRCCS Policlinico, Milan, Italy
  • ,
  • Francesca Novara

      Affiliations

    • Dipartimento di Patologia Umana ed Ereditaria, Sezione Biologia generale e Genetica Medica, University of Pavia, Pavia, Italy
  • ,
  • Cristina Manferdini

      Affiliations

    • Laboratorio di Immunologia e Genetica, Istituti Ortopedici Rizzoli, Bologna, Italy
  • ,
  • Katia Codeluppi

      Affiliations

    • Laboratorio di Immunologia e Genetica, Istituti Ortopedici Rizzoli, Bologna, Italy
  • ,
  • Simona Colla

      Affiliations

    • Ematologia e Centro Trapianti Midollo Osseo, Dipartimento di Medicina Interna e Scienze Biomediche, Azienda Ospedaliero-Universitaria, Parma, Italy
  • ,
  • Monica Crugnola

      Affiliations

    • Ematologia e Centro Trapianti Midollo Osseo, Dipartimento di Medicina Interna e Scienze Biomediche, Azienda Ospedaliero-Universitaria, Parma, Italy
  • ,
  • Manuela Abeltino

      Affiliations

    • Ematologia e Centro Trapianti Midollo Osseo, Dipartimento di Medicina Interna e Scienze Biomediche, Azienda Ospedaliero-Universitaria, Parma, Italy
  • ,
  • Marina Bolzoni

      Affiliations

    • Ematologia e Centro Trapianti Midollo Osseo, Dipartimento di Medicina Interna e Scienze Biomediche, Azienda Ospedaliero-Universitaria, Parma, Italy
  • ,
  • Valentina Sgobba

      Affiliations

    • Ematologia e Centro Trapianti Midollo Osseo, Dipartimento di Medicina Interna e Scienze Biomediche, Azienda Ospedaliero-Universitaria, Parma, Italy
  • ,
  • Andrea Facchini

      Affiliations

    • Laboratorio di Immunologia e Genetica, Istituti Ortopedici Rizzoli, Bologna, Italy
  • ,
  • Giorgio Lambertenghi-Deliliers

      Affiliations

    • Dipartimento di Scienze Mediche, Università di Milano e U.O. Ematologia 1, Fondazione IRCCS Policlinico, Milan, Italy
  • ,
  • Orsetta Zuffardi

      Affiliations

    • Dipartimento di Patologia Umana ed Ereditaria, Sezione Biologia generale e Genetica Medica, University of Pavia, Pavia, Italy
  • ,
  • Vittorio Rizzoli

      Affiliations

    • Ematologia e Centro Trapianti Midollo Osseo, Dipartimento di Medicina Interna e Scienze Biomediche, Azienda Ospedaliero-Universitaria, Parma, Italy
  • ,
  • Antonino Neri

      Affiliations

    • Dipartimento di Scienze Mediche, Università di Milano e U.O. Ematologia 1, Fondazione IRCCS Policlinico, Milan, Italy
  • ,
  • Nicola Giuliani

      Affiliations

    • Ematologia e Centro Trapianti Midollo Osseo, Dipartimento di Medicina Interna e Scienze Biomediche, Azienda Ospedaliero-Universitaria, Parma, Italy
    • Corresponding Author InformationOffprint requests to: Nicola Giuliani, M.D., Ph.D., Department of Internal Medicine and Biomedical Science, University of Parma, Via Gramsci 14, Parma 43100, Italy

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.

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PII: S0301-472X(09)00453-6

doi:10.1016/j.exphem.2009.11.009

Experimental Hematology
Volume 38, Issue 2 , Pages 141-153, February 2010