Multiple myeloma mesenchymal stromal cells: Contribution to myeloma bone disease and therapeutics

Figure 3 Contribution of mesenchymal stromal cells to myeloma bone disease. In MM, MSCs contribute to the development of osteolytic lesions not only because of their reduced osteogenic potential [(1)], but also because they promote OC differentiation and hyperactivation at various levels: pMSCs upregulate the expression of RANKL and reduce that of OPG [(2)]; pMSCs augment the secretion of activin A [(3)]; diminished EphB4-ephrinB2 signaling from pMSCs/OBs to OCs allows osteoclastogenesis [(4)]; increased Wnt5a secretion by pMSCs interacting with myeloma cells enhances RANK expression in OC precursors through Ror2, ultimately increasing their sensibility to RANKL [(5)]. RANKL: Receptor activator of NFκB ligand; NFκB: Nuclear factor-κB; OPG: Osteoprotegerin; RANK: Receptor activator of NFκB; EphrinB2: Ephrin-B2 ligand; EphB4: Eph receptor B4; Ror2: Receptor tyrosine kinase-like orphan receptor 2; MSCs: Mesenchymal stromal cells; MM: Multiple myeloma; OC: Osteoclast; OB: Osteoblast; ALP: Alkaline phosphatase; MM: Multiple myeloma.