Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands

Mark C. Horowitz, Yougen Xi, Kimberly Wilson, Melissa Kacena

Research output: Contribution to journalArticle

171 Citations (Scopus)

Abstract

Skeletal mass is maintained by a balance between cells which resorb bone (osteoclasts) and cells which form bone (osteoblasts). Bone development and growth is an on-going, life-long process. Bone is formed during embryonic life, grows rapidly through childhood, and peaks around 20 years of age (formation exceeds resorption). For humans the skeleton then enters a long period, approximately 40 years, when bone mass remains relatively stable. Skeletal turnover continues but the net effect of resorption and formation on bone mass is zero. For women this ends when they enter menopause and similar bone loss occurs for men, but later in life. These opposite functions are coupled, resorption precedes formation, and osteoblasts, or their precursors, stromal cells, regulate osteoclast formation and activity. Until recently, the molecular nature of this regulation, was poorly understood. However, recent observations have identified members of the TNF family of ligands and receptors as critical regulators of osteoclastogenesis. Osteoprotegerin (OPG) a decoy receptor was first identified. Its ligand, receptor activator of nuclear factor-λB ligand (RANKL), was quickly found, and shown to be expressed on stromal cells and osteoblasts. Its cognate receptor, RANK, was found to be expressed in high levels on osteoclast precursors. The interaction between RANKL and RANK was shown to be required for osteoclast formation. These observations have provided a molecular understanding of the coupling between osteoclastic bone resorption and osteoblastic bone formation. Moreover, they provide a framework on which to base a clear understanding of normal (e.g. postmenopausal osteoporosis and age associated bone loss) and pathologic skeletal changes (e.g. osteopetrosis, glucocorticoid-induced osteoporosis, periodontal disease, bone metastases, Paget's disease, hyperparathyroidism, and rheumatoid arthritis).

Original languageEnglish (US)
Pages (from-to)9-18
Number of pages10
JournalCytokine and Growth Factor Reviews
Volume12
Issue number1
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Tumor Necrosis Factors
Bone Resorption
Osteogenesis
Bone
Osteoclasts
Ligands
Bone and Bones
Osteoblasts
Bone Development
Stromal Cells
Osteopetrosis
Osteitis Deformans
Osteoprotegerin
Postmenopausal Osteoporosis
Hyperparathyroidism
Periodontal Diseases
Cytoplasmic and Nuclear Receptors
Menopause
Skeleton
Glucocorticoids

Keywords

  • Bone resorption
  • Osteoblasts
  • Osteoclastogenesis

ASJC Scopus subject areas

  • Immunology
  • Endocrinology, Diabetes and Metabolism
  • Immunology and Allergy
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands. / Horowitz, Mark C.; Xi, Yougen; Wilson, Kimberly; Kacena, Melissa.

In: Cytokine and Growth Factor Reviews, Vol. 12, No. 1, 2001, p. 9-18.

Research output: Contribution to journalArticle

@article{d70dcdb0fa6a45959cdcca8c8ca45cc0,
title = "Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands",
abstract = "Skeletal mass is maintained by a balance between cells which resorb bone (osteoclasts) and cells which form bone (osteoblasts). Bone development and growth is an on-going, life-long process. Bone is formed during embryonic life, grows rapidly through childhood, and peaks around 20 years of age (formation exceeds resorption). For humans the skeleton then enters a long period, approximately 40 years, when bone mass remains relatively stable. Skeletal turnover continues but the net effect of resorption and formation on bone mass is zero. For women this ends when they enter menopause and similar bone loss occurs for men, but later in life. These opposite functions are coupled, resorption precedes formation, and osteoblasts, or their precursors, stromal cells, regulate osteoclast formation and activity. Until recently, the molecular nature of this regulation, was poorly understood. However, recent observations have identified members of the TNF family of ligands and receptors as critical regulators of osteoclastogenesis. Osteoprotegerin (OPG) a decoy receptor was first identified. Its ligand, receptor activator of nuclear factor-λB ligand (RANKL), was quickly found, and shown to be expressed on stromal cells and osteoblasts. Its cognate receptor, RANK, was found to be expressed in high levels on osteoclast precursors. The interaction between RANKL and RANK was shown to be required for osteoclast formation. These observations have provided a molecular understanding of the coupling between osteoclastic bone resorption and osteoblastic bone formation. Moreover, they provide a framework on which to base a clear understanding of normal (e.g. postmenopausal osteoporosis and age associated bone loss) and pathologic skeletal changes (e.g. osteopetrosis, glucocorticoid-induced osteoporosis, periodontal disease, bone metastases, Paget's disease, hyperparathyroidism, and rheumatoid arthritis).",
keywords = "Bone resorption, Osteoblasts, Osteoclastogenesis",
author = "Horowitz, {Mark C.} and Yougen Xi and Kimberly Wilson and Melissa Kacena",
year = "2001",
doi = "10.1016/S1359-6101(00)00030-7",
language = "English (US)",
volume = "12",
pages = "9--18",
journal = "Cytokine and Growth Factor Reviews",
issn = "1359-6101",
publisher = "Elsevier BV",
number = "1",

}

TY - JOUR

T1 - Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands

AU - Horowitz, Mark C.

AU - Xi, Yougen

AU - Wilson, Kimberly

AU - Kacena, Melissa

PY - 2001

Y1 - 2001

N2 - Skeletal mass is maintained by a balance between cells which resorb bone (osteoclasts) and cells which form bone (osteoblasts). Bone development and growth is an on-going, life-long process. Bone is formed during embryonic life, grows rapidly through childhood, and peaks around 20 years of age (formation exceeds resorption). For humans the skeleton then enters a long period, approximately 40 years, when bone mass remains relatively stable. Skeletal turnover continues but the net effect of resorption and formation on bone mass is zero. For women this ends when they enter menopause and similar bone loss occurs for men, but later in life. These opposite functions are coupled, resorption precedes formation, and osteoblasts, or their precursors, stromal cells, regulate osteoclast formation and activity. Until recently, the molecular nature of this regulation, was poorly understood. However, recent observations have identified members of the TNF family of ligands and receptors as critical regulators of osteoclastogenesis. Osteoprotegerin (OPG) a decoy receptor was first identified. Its ligand, receptor activator of nuclear factor-λB ligand (RANKL), was quickly found, and shown to be expressed on stromal cells and osteoblasts. Its cognate receptor, RANK, was found to be expressed in high levels on osteoclast precursors. The interaction between RANKL and RANK was shown to be required for osteoclast formation. These observations have provided a molecular understanding of the coupling between osteoclastic bone resorption and osteoblastic bone formation. Moreover, they provide a framework on which to base a clear understanding of normal (e.g. postmenopausal osteoporosis and age associated bone loss) and pathologic skeletal changes (e.g. osteopetrosis, glucocorticoid-induced osteoporosis, periodontal disease, bone metastases, Paget's disease, hyperparathyroidism, and rheumatoid arthritis).

AB - Skeletal mass is maintained by a balance between cells which resorb bone (osteoclasts) and cells which form bone (osteoblasts). Bone development and growth is an on-going, life-long process. Bone is formed during embryonic life, grows rapidly through childhood, and peaks around 20 years of age (formation exceeds resorption). For humans the skeleton then enters a long period, approximately 40 years, when bone mass remains relatively stable. Skeletal turnover continues but the net effect of resorption and formation on bone mass is zero. For women this ends when they enter menopause and similar bone loss occurs for men, but later in life. These opposite functions are coupled, resorption precedes formation, and osteoblasts, or their precursors, stromal cells, regulate osteoclast formation and activity. Until recently, the molecular nature of this regulation, was poorly understood. However, recent observations have identified members of the TNF family of ligands and receptors as critical regulators of osteoclastogenesis. Osteoprotegerin (OPG) a decoy receptor was first identified. Its ligand, receptor activator of nuclear factor-λB ligand (RANKL), was quickly found, and shown to be expressed on stromal cells and osteoblasts. Its cognate receptor, RANK, was found to be expressed in high levels on osteoclast precursors. The interaction between RANKL and RANK was shown to be required for osteoclast formation. These observations have provided a molecular understanding of the coupling between osteoclastic bone resorption and osteoblastic bone formation. Moreover, they provide a framework on which to base a clear understanding of normal (e.g. postmenopausal osteoporosis and age associated bone loss) and pathologic skeletal changes (e.g. osteopetrosis, glucocorticoid-induced osteoporosis, periodontal disease, bone metastases, Paget's disease, hyperparathyroidism, and rheumatoid arthritis).

KW - Bone resorption

KW - Osteoblasts

KW - Osteoclastogenesis

UR - http://www.scopus.com/inward/record.url?scp=0035070302&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035070302&partnerID=8YFLogxK

U2 - 10.1016/S1359-6101(00)00030-7

DO - 10.1016/S1359-6101(00)00030-7

M3 - Article

C2 - 11312114

AN - SCOPUS:0035070302

VL - 12

SP - 9

EP - 18

JO - Cytokine and Growth Factor Reviews

JF - Cytokine and Growth Factor Reviews

SN - 1359-6101

IS - 1

ER -