RANK ligand and osteoprotegerin in myeloma bone disease

Blood - Tập 101 - Trang 2094-2098 - 2003
Orhan Sezer, Ulrike Heider, Ivana Zavrski, Christian Alexander Kühne, Lorenz Christian Hofbauer

Tóm tắt

Myeloma bone disease is due to interactions of myeloma cells with the bone marrow microenvironment, and is associated with pathologic fractures, neurologic symptoms and hypercalcemia. Adjacent to myeloma cells, the formation and activation of osteoclasts is increased, which results in enhanced bone resorption. The recent characterization of the essential cytokine of osteoclast cell biology, receptor activator of NF-κB ligand (RANKL) and its antagonist osteoprotegerin (OPG), have led to a detailed molecular and cellular understanding of myeloma bone disease. Myeloma cells induce RANKL expression in bone marrow stromal cells, and direct RANKL expression by myeloma cells may contribute to enhanced osteoclastogenesis in the bone microenvironment in myeloma bone disease. Furthermore, myeloma cells inhibit production and induce degradation of OPG. These effects result in an increased RANKL-to-OPG ratio that favors the formation and activation of osteoclasts. Patients with myeloma bone disease have inappropriately low serum and bone marrow levels of OPG. Specific blockade of RANKL prevented the skeletal complications in various animal models of myeloma, and suppressed bone resorption in a preliminary study of patients with myeloma bone disease.

Tài liệu tham khảo

Bataille, 1997, Multiple myeloma., N Engl J Med., 336, 1657, 10.1056/NEJM199706053362307 Callander, 2001, Myeloma bone disease., Semin Hematol., 38, 276, 10.1016/S0037-1963(01)90020-4 Guise, 2000, Molecular mechanisms of osteolytic bone metastases., Cancer., 88, 2892, 10.1002/1097-0142(20000615)88:12+<2892::AID-CNCR2>3.0.CO;2-Y Roodman, 2001, Biology of osteoclast activation in cancer., J Clin Oncol., 19, 3562, 10.1200/JCO.2001.19.15.3562 Berenson, 1996, Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma., N Engl J Med., 334, 488, 10.1056/NEJM199602223340802 Suda, 1999, Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families., Endocr Rev., 20, 345, 10.1210/edrv.20.3.0367 Teitelbaum, 2000, Bone resorption by osteoclasts., Science., 289, 1504, 10.1126/science.289.5484.1504 Anderson, 1997, A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function., Nature., 390, 175, 10.1038/36593 Lacey, 1998, Osteoprotegerin (OPG) ligand is a cytokine that regulates osteoclast differentiation and activation., Cell., 93, 165, 10.1016/S0092-8674(00)81569-X Hsu, 1999, Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand., Proc Natl Acad Sci U S A., 96, 3540, 10.1073/pnas.96.7.3540 Simonet, 1997, Osteoprotegerin: a novel secreted protein involved in the regulation of bone density., Cell., 89, 309, 10.1016/S0092-8674(00)80209-3 Fuller, 1998, TRANCE is necessary and sufficient for osteoblast-mediated activation of bone resorption in osteoclasts., J Exp Med., 188, 997, 10.1084/jem.188.5.997 Khosla, 2001, The OPG/RANKL/RANK system., Endocrinology., 142, 5050, 10.1210/endo.142.12.8536 Gori, 2000, The expression of osteoprotegerin and RANK ligand and the support of osteoclast formation by stromal-osteoblast lineage cells is developmentally regulated., Endocrinology., 141, 4768, 10.1210/endo.141.12.7840 Kong, 1999, Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand., Nature., 402, 304, 10.1038/46303 Nagai, 2000, Cancer cells responsible for humoral hypercalcemia express mRNA enclosing a secreted form of ODF/TRANCE that induces osteoclast formation., Biochem Biophys Res Commun., 269, 532, 10.1006/bbrc.2000.2314 Nosaka, 2002, Mechanism of hypercalcemia in adult T-cell leukemia: overexpression of receptor activator of nuclear factor κB ligand on adult T-cell leukemia cells., Blood., 99, 634, 10.1182/blood.V99.2.634 Chikatsu, 2000, Interactions between cancer and bone marrow cells induce osteoclast differentiation factor expression and osteoclast-like cell formation in vitro., Biochem Biophys Res Commun., 267, 632, 10.1006/bbrc.1999.2008 Thomas, 1999, Breast cancer cells interact with osteoblasts to support osteoclast formation., Endocrinology., 140, 4451, 10.1210/endo.140.10.7037 Lin, 2001, Bone metastatic LNCaP-derivative C4–2B prostate cancer cell line mineralizes in vitro., Prostate., 47, 212, 10.1002/pros.1065 Brown, 2001, Osteoprotegerin and RANK ligand expression in prostate cancer., Urology., 57, 611, 10.1016/S0090-4295(00)01122-5 Fiumara, 2001, Functional expression of receptor activator of nuclear factor-κB in Hodgkin disease cell lines., Blood., 98, 2784, 10.1182/blood.V98.9.2784 Michigami, 2001, Receptor activator of nuclear factor κB ligand (RANKL) is a key molecule of osteoclast formation for bone metastasis in a newly developed model of human neuroblastoma., Cancer Res., 61, 1637 Sezer, 2002, Human bone marrow myeloma cells express RANKL., J Clin Oncol., 20, 353, 10.1200/JCO.2002.20.1.353 Sezer, 2002, Immunocytochemistry reveals RANKL expression of myeloma cells., Blood., 99, 4646, 10.1182/blood-2002-01-0148 Altamirano, 2001, Malignant multiple myeloma cells expressing RANKL induce the formation of TRAP positive multinucleated cells [abstract]., Blood., 98, 637a Croucher, 2001, Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma., Blood., 98, 3534, 10.1182/blood.V98.13.3534 Pearse, 2001, Multiple myeloma disrupts the TRANCE/osteoprotegerin cytokine axis to stimulate bone destruction and promote tumor progression., Proc Natl Acad Sci U S A., 98, 11581, 10.1073/pnas.201394498 Giuliani, 2001, Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment., Blood., 98, 3527, 10.1182/blood.V98.13.3527 Roux, 2002, RANK (receptor activator of nuclear factor-κB) and RANKL expression in multiple myeloma., Br J Haematol., 117, 86, 10.1046/j.1365-2141.2002.03417.x Giuliani, 2002, Human myeloma cells stimulate the receptor activator of NF-κB ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease., Blood., 100, 4615, 10.1182/blood-2002-04-1121 Standal, 2002, Osteoprotegerin is bound, internalized and degraded by multiple myeloma cells., Blood., 100, 3002, 10.1182/blood-2002-04-1190 Seidel, 2001, Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease., Blood., 98, 2269, 10.1182/blood.V98.7.2269 Lipton, 2002, Serum osteoprotegerin levels in healthy controls and cancer patients., Clin Cancer Res., 8, 2306 Hofbauer, 1999, Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis., Endocrinology., 140, 4382, 10.1210/endo.140.10.7034 Hofbauer, 2001, Effects of immunosuppressants on receptor activator of NF-κB ligand and osteoprotegerin production by human osteoblastic and coronary artery smooth muscle cells., Biochem Biophys Res Commun., 280, 334, 10.1006/bbrc.2000.4130 Viereck, 2002, Bisphosphonates pamidronate and zoledronic acid stimulate osteoprotegerin production by primary human osteoblasts., Biochem Biophys Res Commun., 291, 680, 10.1006/bbrc.2002.6510 Hofbauer, 2001, Serum measurement of osteoprotegerin—clinical relevance and potential applications., Eur J Endocrinol., 145, 681, 10.1530/eje.0.1450681 Brown, 2001, Serum osteoprotegerin levels are increased in patients with advanced prostate cancer., Clin Cancer Res., 7, 2977 Jung, 2001, Osteoprotegerin in serum as a novel marker of bone metastatic spread in prostate cancer., Clin Chem., 47, 2061, 10.1093/clinchem/47.11.2061 Zhang, 2001, Osteoprotegerin inhibits prostate cancer-induced osteoclastogenesis and prevents prostate tumor growth in the bone., J Clin Invest., 107, 1235, 10.1172/JCI11685 Honore, 2000, Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord., Nature Med., 5, 521, 10.1038/74999 Morony, 2001, Osteoprotegerin inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastasis., Cancer Res., 61, 4432 Akatsu, 1998, Osteoclastogenesis inhibitory factor exhibits hypocalcemic effects in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy., Bone., 23, 495, 10.1016/S8756-3282(98)00141-0 Capparelli, 2000, Osteoprotegerin prevents and reverses hypercalcemia in a murine model of humoral hypercalcemia of malignancy., Cancer Res., 60, 783 Oyajobi, 2001, Therapeutic efficacy of a soluble receptor activator of nuclear factor κB-IgG Fc fusion protein in suppressing bone resorption and hypercalcemia in a model of humoral hypercalcemia of malignancy., Cancer Res., 61, 2572 Luger, 2001, Osteoprotegerin diminishes advanced bone cancer pain., Cancer Res., 61, 4038 Yaccoby, 2002, Myeloma interacts with the bone marrow microenvironment to induce osteoclastogenesis and is dependent on osteoclast activity., Br J Haematol., 116, 278, 10.1046/j.1365-2141.2002.03257.x Doran, 2002, Gene transfer of osteoprotegerin-Fc inhibits osteolysis and disease progression in a murine model of multiple myeloma., J Bone Miner Res., 17(suppl 1), 1093 Bekker, 2001, The effect of a single dose of osteoprotegerin in postmenopausal women., J Bone Miner Res., 16, 348, 10.1359/jbmr.2001.16.2.348 Greipp, 2001, A single subcutaneous dose of an osteoprotegerin (OPG) construct (Amgn-0007) causes a profound and sustained decrease of bone resorption comparable to standard intravenous bisphosphonate in patients with multiple myeloma., Blood., 98, 775a Emery, 1998, Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL., J Biol Chem., 273, 14363, 10.1074/jbc.273.23.14363 Choi, 2000, Macrophage inflammatory protein-1alpha is a potential osteoclast stimulatory factor in multiple myeloma., Blood., 96, 671, 10.1182/blood.V96.2.671 Han, 2001, Macrophage inflammatory protein-1α is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor κB ligand., Blood., 97, 3349, 10.1182/blood.V97.11.3349 Abe, 2002, Role for macrophage inflammatory protein (MIP)-1alpha and MIP-1beta in the development of osteolytic lesions in multiple myeloma., Blood., 100, 2195, 10.1182/blood.V100.6.2195.h81802002195_2195_2202 Cozzolino, 1989, Production of interleukin-1 by bone marrow myeloma cells., Blood., 74, 380, 10.1182/blood.V74.1.380.380 Kawano, 1989, Interleukin-1 accelerates autocrine growth of myeloma cells through interleukin-6 in human myeloma., Blood., 73, 2145, 10.1182/blood.V73.8.2145.2145 Bataille, 1989, Serum levels of interleukin-6, a potent myeloma cell growth factor, as a reflection of disease severity in plasma cell dyscrasias., J Clin Invest., 84, 2008, 10.1172/JCI114392 Seidel, 1998, Elevated serum concentrations of hepatocyte growth factor in patients with multiple myeloma., Blood., 91, 806, 10.1182/blood.V91.3.806