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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
Bone resorption in syndromes of the Ras/MAPK pathway
D A Stevenson1, E L Schwarz, J C Carey
1Department of Pediatrics, University of Utah, Salt Lake City, UT 84132, USA. david.stevenson@hsc.utah.edu
Clinical Genetics
|January 6, 2011
Summary
Disorders affecting the Ras/mitogen-activated protein kinase (MAPK) pathway, including Noonan, Costello, and cardiofaciocutaneous syndromes, show increased bone resorption. This suggests the Ras/MAPK pathway is crucial for maintaining bone health.
Area of Science:
- Genetics and Molecular Biology
- Endocrinology and Metabolism
- Skeletal Biology
Background:
- Ras/mitogen-activated protein kinase (MAPK) pathway disorders are linked to skeletal abnormalities like scoliosis and osteopenia.
- Neurofibromatosis type 1 (NF1) patients exhibit heightened osteoclast activity and bone resorption, indicated by elevated urinary pyridinium crosslinks.
Purpose of the Study:
- To investigate whether other Ras/MAPK pathway syndromes also present with increased bone resorption.
- To determine the impact of Ras/MAPK pathway dysregulation on skeletal phenotypes.
Main Methods:
- Urine samples from individuals with Noonan syndrome (n=14), Costello syndrome (n=21), and cardiofaciocutaneous (CFC) syndrome (n=14) were analyzed.
- Pyridinium crosslinks (pyridinoline [Pyd] and deoxypyridinoline [Dpd]) were extracted and quantified using high-performance liquid chromatography.
- Statistical analyses (ANCOVA) compared crosslink levels between patient groups and 99 healthy controls, adjusting for age.
Main Results:
- Deoxypyridinoline (Dpd) and the Dpd/Pyd ratio were significantly elevated in all three syndrome groups compared to controls (p < 0.0001).
- The elevated Dpd levels suggest that collagen degradation primarily originates from bone tissue.
Conclusions:
- The Ras/MAPK signal transduction pathway plays a significant role in regulating bone homeostasis.
- Increased bone resorption is a common feature across multiple Ras/MAPK pathway-associated disorders, contributing to their skeletal phenotypes.
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