Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells

Therese Standal, Carina Seidel, Øyvind Hjertner, Torben Plesner, Ralph D Sanderson, Anders Waage, Magne Borset, Anders Sundan

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Multiple myeloma (MM) is a hematologic malignancy characterized by accumulation of plasma cells in the bone marrow (BM). Bone destruction is a complication of the disease and is usually associated with severe morbidity. The balance between receptor activator of nuclear factor-kappaB (NF-kappaB) ligand and osteoprotegerin (OPG) is of major importance in bone homeostasis. We have recently shown that serum OPG levels are lower in patients with myeloma than in healthy individuals. Here we show that myeloma cells can bind, internalize, and degrade OPG, thereby providing a possible explanation for the lower levels of OPG in the BM of patients with MM. This process is dependent on interaction of OPG with heparan sulfates on the myeloma cells. The results suggest a novel biologic mechanism for the bone disease associated with MM and that treatment of the bone disease with OPG lacking the heparin-binding domain should be considered.

OriginalsprogEngelsk
TidsskriftBlood
Vol/bind100
Udgave nummer8
Sider (fra-til)3002-7
Antal sider6
ISSN0006-4971
DOI
StatusUdgivet - 15. okt. 2002

Fingeraftryk

Osteoprotegerin
Hematologic Neoplasms
Plasma Cells
Homeostasis
Serum

Citer dette

Standal, T., Seidel, C., Hjertner, Ø., Plesner, T., Sanderson, R. D., Waage, A., ... Sundan, A. (2002). Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells. Blood, 100(8), 3002-7. https://doi.org/10.1182/blood-2002-04-1190
Standal, Therese ; Seidel, Carina ; Hjertner, Øyvind ; Plesner, Torben ; Sanderson, Ralph D ; Waage, Anders ; Borset, Magne ; Sundan, Anders. / Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells. I: Blood. 2002 ; Bind 100, Nr. 8. s. 3002-7.
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title = "Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells",
abstract = "Multiple myeloma (MM) is a hematologic malignancy characterized by accumulation of plasma cells in the bone marrow (BM). Bone destruction is a complication of the disease and is usually associated with severe morbidity. The balance between receptor activator of nuclear factor-kappaB (NF-kappaB) ligand and osteoprotegerin (OPG) is of major importance in bone homeostasis. We have recently shown that serum OPG levels are lower in patients with myeloma than in healthy individuals. Here we show that myeloma cells can bind, internalize, and degrade OPG, thereby providing a possible explanation for the lower levels of OPG in the BM of patients with MM. This process is dependent on interaction of OPG with heparan sulfates on the myeloma cells. The results suggest a novel biologic mechanism for the bone disease associated with MM and that treatment of the bone disease with OPG lacking the heparin-binding domain should be considered.",
keywords = "Aged, Biodegradation, Environmental, Biological Transport, Biopsy, Bone Marrow Cells, Female, Glycoproteins, Humans, Immunohistochemistry, Male, Microscopy, Confocal, Multiple Myeloma, Osteoprotegerin, Receptors, Cytoplasmic and Nuclear, Receptors, Tumor Necrosis Factor, Tumor Cells, Cultured",
author = "Therese Standal and Carina Seidel and {\O}yvind Hjertner and Torben Plesner and Sanderson, {Ralph D} and Anders Waage and Magne Borset and Anders Sundan",
year = "2002",
month = "10",
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Standal, T, Seidel, C, Hjertner, Ø, Plesner, T, Sanderson, RD, Waage, A, Borset, M & Sundan, A 2002, 'Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells', Blood, bind 100, nr. 8, s. 3002-7. https://doi.org/10.1182/blood-2002-04-1190

Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells. / Standal, Therese; Seidel, Carina; Hjertner, Øyvind; Plesner, Torben; Sanderson, Ralph D; Waage, Anders; Borset, Magne; Sundan, Anders.

I: Blood, Bind 100, Nr. 8, 15.10.2002, s. 3002-7.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells

AU - Standal, Therese

AU - Seidel, Carina

AU - Hjertner, Øyvind

AU - Plesner, Torben

AU - Sanderson, Ralph D

AU - Waage, Anders

AU - Borset, Magne

AU - Sundan, Anders

PY - 2002/10/15

Y1 - 2002/10/15

N2 - Multiple myeloma (MM) is a hematologic malignancy characterized by accumulation of plasma cells in the bone marrow (BM). Bone destruction is a complication of the disease and is usually associated with severe morbidity. The balance between receptor activator of nuclear factor-kappaB (NF-kappaB) ligand and osteoprotegerin (OPG) is of major importance in bone homeostasis. We have recently shown that serum OPG levels are lower in patients with myeloma than in healthy individuals. Here we show that myeloma cells can bind, internalize, and degrade OPG, thereby providing a possible explanation for the lower levels of OPG in the BM of patients with MM. This process is dependent on interaction of OPG with heparan sulfates on the myeloma cells. The results suggest a novel biologic mechanism for the bone disease associated with MM and that treatment of the bone disease with OPG lacking the heparin-binding domain should be considered.

AB - Multiple myeloma (MM) is a hematologic malignancy characterized by accumulation of plasma cells in the bone marrow (BM). Bone destruction is a complication of the disease and is usually associated with severe morbidity. The balance between receptor activator of nuclear factor-kappaB (NF-kappaB) ligand and osteoprotegerin (OPG) is of major importance in bone homeostasis. We have recently shown that serum OPG levels are lower in patients with myeloma than in healthy individuals. Here we show that myeloma cells can bind, internalize, and degrade OPG, thereby providing a possible explanation for the lower levels of OPG in the BM of patients with MM. This process is dependent on interaction of OPG with heparan sulfates on the myeloma cells. The results suggest a novel biologic mechanism for the bone disease associated with MM and that treatment of the bone disease with OPG lacking the heparin-binding domain should be considered.

KW - Aged

KW - Biodegradation, Environmental

KW - Biological Transport

KW - Biopsy

KW - Bone Marrow Cells

KW - Female

KW - Glycoproteins

KW - Humans

KW - Immunohistochemistry

KW - Male

KW - Microscopy, Confocal

KW - Multiple Myeloma

KW - Osteoprotegerin

KW - Receptors, Cytoplasmic and Nuclear

KW - Receptors, Tumor Necrosis Factor

KW - Tumor Cells, Cultured

U2 - 10.1182/blood-2002-04-1190

DO - 10.1182/blood-2002-04-1190

M3 - Journal article

C2 - 12351414

VL - 100

SP - 3002

EP - 3007

JO - Blood

JF - Blood

SN - 0006-4971

IS - 8

ER -

Standal T, Seidel C, Hjertner Ø, Plesner T, Sanderson RD, Waage A et al. Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells. Blood. 2002 okt 15;100(8):3002-7. https://doi.org/10.1182/blood-2002-04-1190