1,721,223 research outputs found
Myeloma cells and bone marrow osteoblast interactions: Role in the development of osteolytic lesions in multiple myeloma
No full textBone destruction is the hallmark of multiple myeloma (MM) due to the high capacity of malignant plasma cells to induce a severe imbalance of bone remodeling. Growing evidences suggest that MM cell interactions with bone marrow (BM) osteoblast have a critical role in the pathophysiology of osteolytic lesions. Indeed histomorphometric studies have demonstrated that MM patients with osteolytic bone lesions have lower numbers of osteoblasts and decreased bone formation together with osteoclast activation. Recently, the biological mechanisms involved in the osteoblast inhibition induced by MM cells have begun to be elucidated, underlying the main role of the block of osteoblast differentiation in the development of bone lesions. In this article, we summarize the main mechanisms regulating MM cell and osteoblast interactions
New acquisitions in the physiopathology of multiple myeloma: Role of the bone microenvironment
No full textUpdate on the pathogenesis of osteolysis in multiple myeloma patients
No full textMultiple myeloma (MM) is a plasma cell malignancy characterized by the high capacity to induce osteolytic bone lesions that mainly result from an increased bone resorption related to the stimulation of osteoclast recruitment and activity. Although it is known that myeloma cells induce osteoclastic bone resorption, the biological mechanisms involved in the pathophysiology of MM-induced bone resorption have been unclear for several years. Recently, new data seem to elucidate which mechanism is critically involved in the activation of osteoclastic cells in MM. The critical osteoclastogenetic factor RANKL and its soluble antagonist osteoprotegerin (OPG) are the major candidates in the pathophysiology of MM bone disease. Human MM cells induce an imbalance in the RANKL/OPG ratio in the bone marrow environment that triggers the osteoclast formation and activation leading to bone destruction. The role or RANKL/OPG system and other osteoclast stimulating factors in the pathophysiology of MM bone disease are summarized in this update
Angiogenic switch in multiple myeloma
No full textAngiogenesis is the hallmark of cancer. Growing evidence indicates that an imbalance between pro- and anti-angiogenic molecules triggers the angiogenic switch during tumor progression. Several molecules, able to affect vascular formation and function, are now beginning to be elucidated. Recent data indicate that angiogenesis also occurs in hematological malignancies. In multiple myeloma it has been demonstrated that patients with active disease have an increase in bone marrow angiogenesis correlated with the progression of disease and an adverse prognosis. The pathophysiology of myeloma-induced angiogenesis is complex and involves either the direct production of angiogenic molecules by myeloma cells or their induction in the microenvironment. In this review we have focalized our attention on the main factors involved in the angiogenic switch that occurs in MM patients
Osteogenic differentiation of mesenchymal stem cells in multiple myeloma: identification of potential therapeutic targets
No full textObjective. 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 cell
New insight in the mechanism of osteoclast activation and formation in multiple myeloma: focus on the receptor activator of NF-kappaB ligand (RANKL)
No full textThe increase of osteoclast activation and formation is mainly involved in the development of the osteolytic bone lesions that characterize multiple myeloma (MM) patients. The mechanisms by which myeloma cells induce bone resorption have not been clear for many years. Recently, new evidence has elucidated which factors are critically involved in the activation of osteoclastic cells in MM. The potential role of the critical osteoclastogenic factor, the receptor activator of NF-kappaB ligand (RANKL), and its soluble antagonist osteoprotegerin (OPG) in the activation of bone resorption in MM is summarized in this review. It has been demonstrated that human MM cells induce an imbalance in the bone marrow environment of the RANKL/OPG ratio in favor of RANKL that triggers the osteoclast formation and activation leading to bone destruction. The direct production of the chemokine macrophage inflammatory protein-1 alpha (MIP-1alpha) by myeloma cells, in combination with the RANKL induction in BM stromal cells in response to myeloma cells, are critical in osteoclast activation and osteoclastogenesis
Multiple myeloma bone disease: pathophysiology of osteoblast inhibition
No full textMultiple myeloma (MM) is a plasma cell
malignancy characterized by a high capacity
to induce osteolytic bone lesions.
Bone destruction in MM results from increased
osteoclast formation and activity
that occur in close proximity to myeloma
cells. However, histomorphometric studies
have demonstrated that MM patients
with osteolytic bone lesions have lower
numbers of osteoblasts and decreased
bone formation. This impaired bone formation
plays a critical role in the bonedestructive
process. Recently, the biologic
mechanisms involved in the
osteoblast inhibition induced by MM cells
have begun to be elucidated. In this article,
the pathophysiology underlying osteoblast
inhibition in MM is reviewed
Angiopoietin-1 and myeloma-induced angiogenesis
No full textMultiple myeloma (MM) is a plasma cell malignancy characterized by an increase of the bone marrow angiogenesis. Angiopoietin-1 (Ang-1) is a critical factor in the regulation of physiological and pathological vessel formation that acts by binding to a specific receptor Tie2 expressed on endothelial cells. Recent evidences indicate that human MM cells produce Ang-1 and up-regulate its receptor Tie2 in bone marrow endothelial cells. An overexpression of Ang-1 has been also found in MM cells as compared to normal plasma cells. The correlation between Ang-1 expression and BM angiogenesis, demonstrated in MM patients, and the inhibitory effect of Tie2 blocking on MM-induced vessel formation suggest that Ang-1 production by MM cells is critically involved in the angiogenic process in MM. In this review we focalize our attention on Ang-1/Tie2 system and its role in MM-induced angiogenesis
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