Cited by 6,670Bone Metabolism and DiseasesBone health and osteoporosis researchBone and Dental Protein Studies

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Osteoclast differentiation and activation

Boyle, William J., Simonet, W. Scott, Lacey, David L.·2003·Nature

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Abstract

Osteoclasts are specialized cells derived from the monocyte/macrophage haematopoietic lineage that develop and adhere to bone matrix, then secrete acid and lytic enzymes that degrade it in a specialized, extracellular compartment. Discovery of the RANK signalling pathway in the osteoclast has provided insight into the mechanisms of osteoclastogenesis and activation of bone resorption, and how hormonal signals impact bone structure and mass. Further study of this pathway is providing the molecular basis for developing therapeutics to treat osteoporosis and other diseases of bone loss.

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Background
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Background
Resveratrol-mediated SIRT-1 Interactions with p300 Modulate Receptor Activator of NF-κB Ligand (RANKL) Activation of NF-κB Signaling and Inhibit Osteoclastogenesis in Bone-derived Cells
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BackgroundInfluential
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BackgroundMethod
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BackgroundInfluential
Endothelial proteolytic activity and interaction with non-resorbing osteoclasts mediate bone elongation
Romeo, S. G., Alawi, K. M., Rodrigues, J., Singh, A., Kusumbe, A. P., & Ramasamy, S. K. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0304-7 · Cited by 213
Loureirin B suppresses RANKL-induced osteoclastogenesis and ovariectomized osteoporosis via attenuating NFATc1 and ROS activities
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Bone marrow adipogenic lineage precursors promote osteoclastogenesis in bone remodeling and pathologic bone loss
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“Osteoclast differentiation predominantly depends on RANKL signaling (encoded by Tnfsf11 gene), a type II transmembrane protein of the TNF superfamily, and is modulated by other cytokines and growth factors (3).”
Background
SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK
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“21 RANKL induces OCL differentiation in the presence of M-CSF”
Background
Inhibition of RANKL blocks skeletal tumor progression and improves survival in a mouse model of breast cancer bone metastasis
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“The level of osteoclastogenesis and, therefore, bone resorption is primarily regulated by the levels of RANKL, which is expressed almost exclusively within the bone marrow stromal cell compartment and is induced by most hormones and factors that stimulate bone resorption [10], including the major factors associated wi…”
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Novel approaches to target the microenvironment of bone metastasis
Hofbauer, L. C., Bözec, A., Rauner, M., Jakob, F. J., Perner, S., & Pantel, K. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00499-9 · Cited by 223
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“…studies have identified transcription factors, growth factors and their receptors, hormones and intracellular signaling molecules that affect one or the other arm of bone remodeling at the level of cell differentiation, proliferation, or function (Boyle et al., 2003; Teitelbaum and Ross, 2003).”
Background
RANK ligand signaling modulates the matrix metalloproteinase-9 gene expression during osteoclast differentiation
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Circulating Osteoprotegerin Levels and Long-Term Prognosis in Patients With Acute Coronary Syndromes
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“The ability of OPG to reflect t ANKL/RANK activity, a potential important mediator in eft ventricular remodeling and a more general marker of nflammation, could contribute to its prognostic impact.”
BackgroundInfluential
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“To form mature, boneresorbing osteoclasts, the presence of macrophage colonystimulating factor (M-CSF) and RANKL is essential [70].”
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Background
Homocysteine Enhances Bone Resorption by Stimulation of Osteoclast Formation and Activity Through Increased Intracellular ROS Generation
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“It is generally accepted that two critical steps occur in osteoclast formation: commitment of progenitor cells to osteoclast precursor cells, and fusion of the TRACP mononuclear cells to form multinucleated osteoclasts.((26)) We found that incubation of BMCs with Hcy for days 3–5 of the culture period stimulated osteo…”
BackgroundInfluential
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Background
Molecular mechanisms and clinical management of cancer bone metastasis
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Background
The Fos‐related antigen Fra‐1 is an activator of bone matrix formation
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Background
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“Many genes and factors have been shown to positively or negatively regulate osteoclastogenesis and osteoclast activation directly and/or indirectly through the interactions between the osteoblasts/bone marrow stromal cells and osteoclast precursors.((15,16)) These genes and factors exert their effects at various stage…”
Background
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Background
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Background
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“Recombinant M-CSF and GST-RANKL were generous gifts from Steven Teitelbaum (Washington University School of Medicine, St. Louis, Missouri, USA).”
BackgroundInfluential
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Background
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“Individuals with this disease are also typically short in stature [46].”
Background
Poly(lactide-co-glycolide)/hydroxyapatite nanofibrous scaffolds fabricated by electrospinning for bone tissue engineering
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“To summarize how RANKL signals the cell briefly, the binding of RANKL to its receptor RANK results in the recruitment of TNF receptor-associated factor (TRAF)-family proteins such as TRAF6, which activates NF-kB and c-Jun Nterminal kinase (JNK) pathways (8, 15).”
Background
Pathogenesis of osteoblastic bone metastases from prostate cancer
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“tivator of osteoclast differentiation, and osteoprotegerin, a soluble decoy receptor that inhibits RANKL.(68,69) An increase in the level of serum osteoprotegerin (OPG) has”
Background
Melatonin effects on bone: potential use for the prevention and treatment for osteopenia, osteoporosis, and periodontal disease and for use in bone‐grafting procedures
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Fat’s loss is bone’s gain
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Selective Regulation of MAPK Signaling Mediates RANKL-dependent Osteoclast Differentiation
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Regulation of osteoclast function and bone mass by RAGE
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Authors: Boyle, W. J., Simonet, W. S., & Lacey, D. L.
Affiliations: Amgen (United States) (US)
Corresponding author: Boyle, William J.
ORCID: Boyle, William J.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2003-05
Volume: 423
Issue: 6937
Pages: 337-342
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature01658
OpenAlex: W2093252878
Cited by: 6,670
References: 77
Citations by year: 2026: 240 · 2025: 269 · 2024: 294 · 2023: 357 · 2022: 349 · 2021: 404 · 2020: 376 · 2019: 381 · 2018: 371 · 2017: 324 · 2016: 311 · 2015: 332 · 2014: 352 · 2013: 315 · 2012: 336
FWCI: 11.72
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Bone and Dental Protein Studies
Keywords: osteoclasts, osteoclastogenesis, bone resorption, monocyte/macrophage lineage, bone matrix degradation, hormonal regulation of bone, osteoporosis
MeSH terms: Animals, Bone Resorption, Carrier Proteins, Cell Differentiation, Glycoproteins, Humans, Membrane Glycoproteins, Osteoclasts, Osteoporosis, Signal Transduction, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B

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