Osteoclasts

Potential target for blocking microenvironmental support of myeloma

Deborah L. Galson, Sonia D'Souza, G. David Roodman

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Multiple myeloma (MM) bone disease is a major contributor to the morbidity and mortality of MM patients due to pathological fractures. The MM cells interact with the cells of the bone microenvironment to both generate bone lesions as a result of enhanced induction of osteoclastogenesis and prevent reactive new bone formation to heal the lesions by repressing osteoblast activity. The MM stimulated osteoclasts (OCLs) not only generate bone lesions, but also interact with the myeloma cells to promote the proliferation and survival of the MM cells through the generation of interleukin-6 (IL-6), osteopontin, fibroblast activation protein, BAFF, APRIL, and annexin II. These MM-supportive OCL products present therapeutic opportunities. Further, the enhanced bone resorption by OCLs releases immobilized growth factors from the bone matrix that both support the MM cells and further stimulate OCL differentiation in a vicious cycle. Hence, targeting osteoclast activity may inhibit myeloma growth. Therefore, bisphosphonates have been investigated for their anti-tumor affects. The MM cells increase osteoclast activity both directly and by stimulation of microenvironmental production of RANKL, MIP-1α, TNF-α and interleukins IL-1β, IL-3 and IL-6. These are therefore also possible therapeutic targets to inhibit myeloma bone disease.

Original languageEnglish (US)
Title of host publicationAdvances in Biology and Therapy of Multiple Myeloma: Volume 1: Basic Science
PublisherSpringer New York
Pages169-185
Number of pages17
ISBN (Print)9781461446668, 9781461446651
DOIs
StatePublished - Jan 1 2013

Fingerprint

Osteoclasts
Multiple Myeloma
Bone Diseases
Tumor Necrosis Factor Ligand Superfamily Member 13
Interleukin-1
Osteogenesis
Bone and Bones
Interleukin-6
Annexin A2
Cellular Microenvironment
Spontaneous Fractures
Bone Matrix
Osteopontin
Interleukin-3
Diphosphonates
Bone Resorption
Osteoblasts
Intercellular Signaling Peptides and Proteins
Fibroblasts
Morbidity

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Galson, D. L., D'Souza, S., & Roodman, G. D. (2013). Osteoclasts: Potential target for blocking microenvironmental support of myeloma. In Advances in Biology and Therapy of Multiple Myeloma: Volume 1: Basic Science (pp. 169-185). Springer New York. https://doi.org/10.1007/978-1-4614-4666-8_9

Osteoclasts : Potential target for blocking microenvironmental support of myeloma. / Galson, Deborah L.; D'Souza, Sonia; Roodman, G. David.

Advances in Biology and Therapy of Multiple Myeloma: Volume 1: Basic Science. Springer New York, 2013. p. 169-185.

Research output: Chapter in Book/Report/Conference proceedingChapter

Galson, DL, D'Souza, S & Roodman, GD 2013, Osteoclasts: Potential target for blocking microenvironmental support of myeloma. in Advances in Biology and Therapy of Multiple Myeloma: Volume 1: Basic Science. Springer New York, pp. 169-185. https://doi.org/10.1007/978-1-4614-4666-8_9
Galson DL, D'Souza S, Roodman GD. Osteoclasts: Potential target for blocking microenvironmental support of myeloma. In Advances in Biology and Therapy of Multiple Myeloma: Volume 1: Basic Science. Springer New York. 2013. p. 169-185 https://doi.org/10.1007/978-1-4614-4666-8_9
Galson, Deborah L. ; D'Souza, Sonia ; Roodman, G. David. / Osteoclasts : Potential target for blocking microenvironmental support of myeloma. Advances in Biology and Therapy of Multiple Myeloma: Volume 1: Basic Science. Springer New York, 2013. pp. 169-185
@inbook{16fc627b75a742ca91cb315fd11e2edf,
title = "Osteoclasts: Potential target for blocking microenvironmental support of myeloma",
abstract = "Multiple myeloma (MM) bone disease is a major contributor to the morbidity and mortality of MM patients due to pathological fractures. The MM cells interact with the cells of the bone microenvironment to both generate bone lesions as a result of enhanced induction of osteoclastogenesis and prevent reactive new bone formation to heal the lesions by repressing osteoblast activity. The MM stimulated osteoclasts (OCLs) not only generate bone lesions, but also interact with the myeloma cells to promote the proliferation and survival of the MM cells through the generation of interleukin-6 (IL-6), osteopontin, fibroblast activation protein, BAFF, APRIL, and annexin II. These MM-supportive OCL products present therapeutic opportunities. Further, the enhanced bone resorption by OCLs releases immobilized growth factors from the bone matrix that both support the MM cells and further stimulate OCL differentiation in a vicious cycle. Hence, targeting osteoclast activity may inhibit myeloma growth. Therefore, bisphosphonates have been investigated for their anti-tumor affects. The MM cells increase osteoclast activity both directly and by stimulation of microenvironmental production of RANKL, MIP-1α, TNF-α and interleukins IL-1β, IL-3 and IL-6. These are therefore also possible therapeutic targets to inhibit myeloma bone disease.",
author = "Galson, {Deborah L.} and Sonia D'Souza and Roodman, {G. David}",
year = "2013",
month = "1",
day = "1",
doi = "10.1007/978-1-4614-4666-8_9",
language = "English (US)",
isbn = "9781461446668",
pages = "169--185",
booktitle = "Advances in Biology and Therapy of Multiple Myeloma: Volume 1: Basic Science",
publisher = "Springer New York",

}

TY - CHAP

T1 - Osteoclasts

T2 - Potential target for blocking microenvironmental support of myeloma

AU - Galson, Deborah L.

AU - D'Souza, Sonia

AU - Roodman, G. David

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Multiple myeloma (MM) bone disease is a major contributor to the morbidity and mortality of MM patients due to pathological fractures. The MM cells interact with the cells of the bone microenvironment to both generate bone lesions as a result of enhanced induction of osteoclastogenesis and prevent reactive new bone formation to heal the lesions by repressing osteoblast activity. The MM stimulated osteoclasts (OCLs) not only generate bone lesions, but also interact with the myeloma cells to promote the proliferation and survival of the MM cells through the generation of interleukin-6 (IL-6), osteopontin, fibroblast activation protein, BAFF, APRIL, and annexin II. These MM-supportive OCL products present therapeutic opportunities. Further, the enhanced bone resorption by OCLs releases immobilized growth factors from the bone matrix that both support the MM cells and further stimulate OCL differentiation in a vicious cycle. Hence, targeting osteoclast activity may inhibit myeloma growth. Therefore, bisphosphonates have been investigated for their anti-tumor affects. The MM cells increase osteoclast activity both directly and by stimulation of microenvironmental production of RANKL, MIP-1α, TNF-α and interleukins IL-1β, IL-3 and IL-6. These are therefore also possible therapeutic targets to inhibit myeloma bone disease.

AB - Multiple myeloma (MM) bone disease is a major contributor to the morbidity and mortality of MM patients due to pathological fractures. The MM cells interact with the cells of the bone microenvironment to both generate bone lesions as a result of enhanced induction of osteoclastogenesis and prevent reactive new bone formation to heal the lesions by repressing osteoblast activity. The MM stimulated osteoclasts (OCLs) not only generate bone lesions, but also interact with the myeloma cells to promote the proliferation and survival of the MM cells through the generation of interleukin-6 (IL-6), osteopontin, fibroblast activation protein, BAFF, APRIL, and annexin II. These MM-supportive OCL products present therapeutic opportunities. Further, the enhanced bone resorption by OCLs releases immobilized growth factors from the bone matrix that both support the MM cells and further stimulate OCL differentiation in a vicious cycle. Hence, targeting osteoclast activity may inhibit myeloma growth. Therefore, bisphosphonates have been investigated for their anti-tumor affects. The MM cells increase osteoclast activity both directly and by stimulation of microenvironmental production of RANKL, MIP-1α, TNF-α and interleukins IL-1β, IL-3 and IL-6. These are therefore also possible therapeutic targets to inhibit myeloma bone disease.

UR - http://www.scopus.com/inward/record.url?scp=84948154515&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84948154515&partnerID=8YFLogxK

U2 - 10.1007/978-1-4614-4666-8_9

DO - 10.1007/978-1-4614-4666-8_9

M3 - Chapter

SN - 9781461446668

SN - 9781461446651

SP - 169

EP - 185

BT - Advances in Biology and Therapy of Multiple Myeloma: Volume 1: Basic Science

PB - Springer New York

ER -