Osteogenic differentiation of mesenchymal stem cells in multiple myeloma: Identification of potential therapeutic targets
Received 16 March 2009; received in revised form 10 April 2009; accepted 20 April 2009. published online 27 April 2009.
Objective
Osteogenic differentiation of mesenchymal cells toward osteoprogenitor and osteoblastic cells is tightly regulated by several growth and transcription factors at the molecular level. In this article, we focus on the biological mechanisms involved in the osteoblast inhibition induced by myeloma cells.
Materials and Methods
Current research on the mechanisms regulating myeloma cell and osteoprogenitor cells interactions and on potential therapeutic targets to treat multiple myeloma bone disease is reviewed.
Results
Runt-related transcription factor 2 is critically involved in this process along with a large number of nuclear coregulators. Wnt signaling has been recently identified as a critical pathway involved in the regulation of osteoblastogenesis. The impairment of osteogenic differentiation in mesenchymal stem cells occurs in multiple myeloma due to the capacity of malignant plasma cells to suppress the osteogenic differentiation of mesenchymal cells either through the cell contact or the release of soluble factors as interleukin-7, hepatocyte growth factor, interleukin-3, and Wnt inhibitors.
Conclusion
Runt-related transcription factor 2 and Wnt pathways could be therapeutic targets in the treatment of multiple myeloma bone disease to counterbalance the block of osteogenic differentiation induced by multiple myeloma cells.
Cattedra di Ematologia e CTMO, Azienda Ospedaliero-Universitaria, Parma, Italy
Offprint requests to: Nicola Giuliani, M.D., Ph.D., Department of Hematology and BMT Center, University of Parma, via Gramsci 14, 43100 Parma, Italy
ABSTRACT