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Updated: Dec 8, 2025
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A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
Published on: March 15, 2018
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Genetic disorders associated with the RANKL/OPG/RANK pathway
Jing-Yi Xue1,2, Shiro Ikegawa3, Long Guo4
1Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, 4-6-1 Minato-ku, Tokyo, 108-8639, Japan.
Journal of Bone and Mineral Metabolism
|September 17, 2020
Summary
Mutations in the RANKL/OPG/RANK pathway genes (TNFSF11, TNFRSF11B, TNFRSF11A) cause skeletal disorders. These genetic defects lead to either increased bone turnover or elevated bone density, affecting bone metabolism and morphology.
Area of Science:
- Genetics
- Bone Biology
- Molecular Signaling
Background:
- The RANKL/OPG/RANK pathway is crucial for osteoclast regulation.
- Mutations in key genes (TNFSF11, TNFRSF11B, TNFRSF11A) disrupt bone metabolism.
- Nine monogenic skeletal diseases are linked to these gene mutations.
Purpose of the Study:
- To review genetic disorders associated with the RANKL/OPG/RANK pathway.
- To detail genotype-phenotype correlations in TNFRSF11A-related diseases.
- To categorize skeletal diseases based on mutation effects on osteoclastogenesis.
Main Methods:
- Literature review of genetic skeletal disorders.
- Analysis of genotype-phenotype associations.
- Classification of diseases based on pathogenic mechanisms.
Main Results:
- Two main disease types identified: increased osteoclastogenesis (e.g., Paget's disease) and decreased osteoclastogenesis (e.g., osteopetrosis).
- Specific mutations in TNFSF11, TNFRSF11B, and TNFRSF11A lead to distinct skeletal pathologies.
- Detailed genotype-phenotype data for TNFRSF11A-associated diseases are highlighted.
Conclusions:
- Genetic variations in the RANKL/OPG/RANK pathway underpin diverse skeletal disorders.
- Understanding these genetic links is vital for diagnosing and potentially treating bone diseases.
- Further research on genotype-phenotype associations can refine disease classification and management.
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