Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma.

Multiple myeloma is a B-cell malignancy characterized by the accumulation of plasma cells in the bone marrow and the development of osteolytic bone disease. The present study demonstrates that myeloma cells express the critical osteoclastogenic factor RANKL (the ligand for receptor activator of NF-k...

Description complète

Détails bibliographiques
Auteurs principaux: Croucher, P, Shipman, C, Lippitt, J, Perry, M, Asosingh, K, Hijzen, A, Brabbs, A, van Beek, E, Holen, I, Skerry, T, Dunstan, C, Russell, G, Van Camp, B, Vanderkerken, K
Format: Journal article
Langue:English
Publié: 2001
_version_ 1826281548308021248
author Croucher, P
Shipman, C
Lippitt, J
Perry, M
Asosingh, K
Hijzen, A
Brabbs, A
van Beek, E
Holen, I
Skerry, T
Dunstan, C
Russell, G
Van Camp, B
Vanderkerken, K
author_facet Croucher, P
Shipman, C
Lippitt, J
Perry, M
Asosingh, K
Hijzen, A
Brabbs, A
van Beek, E
Holen, I
Skerry, T
Dunstan, C
Russell, G
Van Camp, B
Vanderkerken, K
author_sort Croucher, P
collection OXFORD
description Multiple myeloma is a B-cell malignancy characterized by the accumulation of plasma cells in the bone marrow and the development of osteolytic bone disease. The present study demonstrates that myeloma cells express the critical osteoclastogenic factor RANKL (the ligand for receptor activator of NF-kappa B). Injection of 5T2MM myeloma cells into C57BL/KaLwRij mice resulted in the development of bone disease characterized by a significant decrease in cancellous bone volume in the tibial and femoral metaphyses, an increase in osteoclast formation, and radiologic evidence of osteolytic bone lesions. Dual-energy x-ray absorptiometry demonstrated a decrease in bone mineral density (BMD) at each of these sites. Treatment of mice with established myeloma with recombinant osteoprotegerin (OPG) protein, the soluble decoy receptor for RANKL, prevented the development of lytic bone lesions. OPG treatment was associated with preservation of cancellous bone volume and inhibition of osteoclast formation. OPG also promoted an increase in femoral, tibial, and vertebral BMD. These data suggest that the RANKL/RANK/OPG system may play a critical role in the development of osteolytic bone disease in multiple myeloma and that targeting this system may have therapeutic potential.
first_indexed 2024-03-07T00:30:27Z
format Journal article
id oxford-uuid:7f9b546c-c0f0-4c3c-a7b4-832c6c427f34
institution University of Oxford
language English
last_indexed 2024-03-07T00:30:27Z
publishDate 2001
record_format dspace
spelling oxford-uuid:7f9b546c-c0f0-4c3c-a7b4-832c6c427f342022-03-26T21:17:59ZOsteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7f9b546c-c0f0-4c3c-a7b4-832c6c427f34EnglishSymplectic Elements at Oxford2001Croucher, PShipman, CLippitt, JPerry, MAsosingh, KHijzen, ABrabbs, Avan Beek, EHolen, ISkerry, TDunstan, CRussell, GVan Camp, BVanderkerken, KMultiple myeloma is a B-cell malignancy characterized by the accumulation of plasma cells in the bone marrow and the development of osteolytic bone disease. The present study demonstrates that myeloma cells express the critical osteoclastogenic factor RANKL (the ligand for receptor activator of NF-kappa B). Injection of 5T2MM myeloma cells into C57BL/KaLwRij mice resulted in the development of bone disease characterized by a significant decrease in cancellous bone volume in the tibial and femoral metaphyses, an increase in osteoclast formation, and radiologic evidence of osteolytic bone lesions. Dual-energy x-ray absorptiometry demonstrated a decrease in bone mineral density (BMD) at each of these sites. Treatment of mice with established myeloma with recombinant osteoprotegerin (OPG) protein, the soluble decoy receptor for RANKL, prevented the development of lytic bone lesions. OPG treatment was associated with preservation of cancellous bone volume and inhibition of osteoclast formation. OPG also promoted an increase in femoral, tibial, and vertebral BMD. These data suggest that the RANKL/RANK/OPG system may play a critical role in the development of osteolytic bone disease in multiple myeloma and that targeting this system may have therapeutic potential.
spellingShingle Croucher, P
Shipman, C
Lippitt, J
Perry, M
Asosingh, K
Hijzen, A
Brabbs, A
van Beek, E
Holen, I
Skerry, T
Dunstan, C
Russell, G
Van Camp, B
Vanderkerken, K
Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma.
title Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma.
title_full Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma.
title_fullStr Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma.
title_full_unstemmed Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma.
title_short Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma.
title_sort osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma
work_keys_str_mv AT croucherp osteoprotegerininhibitsthedevelopmentofosteolyticbonediseaseinmultiplemyeloma
AT shipmanc osteoprotegerininhibitsthedevelopmentofosteolyticbonediseaseinmultiplemyeloma
AT lippittj osteoprotegerininhibitsthedevelopmentofosteolyticbonediseaseinmultiplemyeloma
AT perrym osteoprotegerininhibitsthedevelopmentofosteolyticbonediseaseinmultiplemyeloma
AT asosinghk osteoprotegerininhibitsthedevelopmentofosteolyticbonediseaseinmultiplemyeloma
AT hijzena osteoprotegerininhibitsthedevelopmentofosteolyticbonediseaseinmultiplemyeloma
AT brabbsa osteoprotegerininhibitsthedevelopmentofosteolyticbonediseaseinmultiplemyeloma
AT vanbeeke osteoprotegerininhibitsthedevelopmentofosteolyticbonediseaseinmultiplemyeloma
AT holeni osteoprotegerininhibitsthedevelopmentofosteolyticbonediseaseinmultiplemyeloma
AT skerryt osteoprotegerininhibitsthedevelopmentofosteolyticbonediseaseinmultiplemyeloma
AT dunstanc osteoprotegerininhibitsthedevelopmentofosteolyticbonediseaseinmultiplemyeloma
AT russellg osteoprotegerininhibitsthedevelopmentofosteolyticbonediseaseinmultiplemyeloma
AT vancampb osteoprotegerininhibitsthedevelopmentofosteolyticbonediseaseinmultiplemyeloma
AT vanderkerkenk osteoprotegerininhibitsthedevelopmentofosteolyticbonediseaseinmultiplemyeloma