Related Experiment Video

Updated: Aug 9, 2026

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
09:37

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

[Monoclonal antibody targeting RANKL as a therapy for cancer-induced bone diseases]

William Dougall1, Michelle Chaisson

  • 1Amgen Inc. Washington, Department of Cancer Biology, Seattle, WA, USA.

Clinical Calcium
|April 4, 2006
PubMed

Insights

Receptor activator of NF-kappaB ligand (RANKL) drives bone loss. Denosumab, a RANKL inhibitor, shows promise in early trials for treating bone disorders like cancer-induced bone disease.

Area of Science:

  • Biochemistry and Molecular Biology
  • Genomics
  • Immunology

Context:

  • The RANK/RANKL/OPG signaling pathway is crucial for bone mass regulation.
  • RANKL is essential for osteoclast development and bone resorption.
  • Genomic discovery led to understanding this critical bone metabolism axis.

Purpose:

  • To explore the role of the RANK/RANKL/OPG axis in bone metabolism.
  • To investigate denosumab, a RANKL-inhibiting monoclonal antibody, as a therapeutic agent.
  • To evaluate the safety and efficacy of denosumab in preclinical and early clinical settings.

Summary:

  • Receptor activator of NF-kappaB ligand (RANKL) is a key mediator of osteoclastogenesis and bone loss.
  • Osteoprotegerin (OPG) is a natural inhibitor of RANKL.
  • Denosumab, a fully human monoclonal antibody, targets and neutralizes RANKL, mimicking OPG's function.

Impact:

  • Established the RANK/RANKL/OPG axis as a central regulator of bone mass.
  • Provided the rationale for developing targeted RANKL inhibitors for bone diseases.
  • Early clinical trials indicate denosumab effectively suppresses bone turnover and is well-tolerated, warranting further investigation.

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...