title: The osteoblastic niche in the context of multiple myeloma.
abstract: The osteoblastic niche has a critical role in the regulation of hemopoietic stem cell (HSC) quiescence and self-renewal and in the support of hematopoiesis. Several mechanisms are involved in the crosstalk between stem cells and osteoblasts, including soluble cytokines, adhesion molecules, and signal pathways such as the wingless-Int (Wnt), Notch, and parathyroid hormone pathways. According to the most recent evidence, there is an overlap between osteoblastic and perivascular niches that affects HSC function involving mesenchymal stromal and endothelial cells and a gradient of oxygen regulated by hypoxia inducible factor (HIF)-1α. Derived from plasma cells, multiple myeloma (MM) is a hematopoietic malignancy characterized by a peculiar dependency on the bone microenvironment. Quiescent MM cells may reside in the osteoblastic niche for protection from apoptotic stimuli; in turn, MM cells suppress osteoblast formation and function, leading to impairment of bone formation and the development of osteolytic lesions. Several recent studies have investigated the mechanisms involved in the relationship between osteoblasts and MM cells and identified potential therapeutic targets in the osteoblastic niche, including the HIF-1α, Runx2, and Wnt (both canonical and noncanonical) signaling pathways.
authors.affiliation: Myeloma Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors.forename: Denise
authors.initials: D
authors.lastname: Toscani
authors.forename: Marina
authors.initials: M
authors.lastname: Bolzoni
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Accardi
authors.forename: Franco
authors.initials: F
authors.lastname: Aversa
authors.forename: Nicola
authors.initials: N
authors.lastname: Giuliani
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D010006:Osteoblasts / Q000473:pathology* / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
keywords: Toscani, D., M. Bolzoni, F. Accardi, et al. 2014. The osteoblastic niche in the context of multiple myeloma. In “MARROW,” ed. by M. Zaidi. Ann. N.Y. Acad. Sci. xxxx: 1-18.; Wnt signaling; bone disease; myeloma; osteoblast; osteocyte