Related Experiment Video
Updated: Apr 23, 2026
Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
Statin treatment rescues FGFR3 skeletal dysplasia phenotypes
Akihiro Yamashita1, Miho Morioka1, Hiromi Kishi1
1Cell Induction and Regulation Field, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.
Abstract:
Gain-of-function mutations in the fibroblast growth factor receptor 3 gene (FGFR3) result in skeletal dysplasias, such as thanatophoric dysplasia and achondroplasia (ACH). The lack of disease models using human cells has hampered the identification of a clinically effective treatment for these diseases. Here we show that statin treatment can rescue patient-specific induced pluripotent stem cell (iPSC) models and a mouse model of FGFR3 skeletal dysplasia. We converted fibroblasts from thanatophoric dysplasia type I (TD1) and ACH patients into iPSCs. The chondrogenic differentiation of TD1 iPSCs and ACH iPSCs resulted in the formation of degraded cartilage. We found that statins could correct the degraded cartilage in both chondrogenically differentiated TD1 and ACH iPSCs. Treatment of ACH model mice with statin led to a significant recovery of bone growth. These results suggest that statins could represent a medical treatment for infants and children with TD1 and ACH.
Insights
Statins may treat skeletal dysplasias like achondroplasia by improving cartilage in patient stem cells and bone growth in mice. This offers hope for treating these rare genetic disorders.
Area of Science:
- Genetics and Developmental Biology
- Stem Cell Research
- Pharmacology
Background:
- Gain-of-function mutations in fibroblast growth factor receptor 3 (FGFR3) cause skeletal dysplasias, including thanatophoric dysplasia (TD1) and achondroplasia (ACH).
- A lack of human cell-based disease models has hindered the development of effective treatments for these conditions.
Purpose of the Study:
- To investigate the therapeutic potential of statins in patient-specific induced pluripotent stem cell (iPSC) models and a mouse model of FGFR3 skeletal dysplasia.
- To determine if statin treatment can rescue cellular and in vivo phenotypes associated with TD1 and ACH.
Main Methods:
- Fibroblasts from TD1 and ACH patients were converted into iPSCs.
- iPSCs underwent chondrogenic differentiation to model cartilage development.
- Patient-derived iPSC-derived cartilage and an ACH mouse model were treated with statins.
- Bone growth recovery in the mouse model was assessed.
Main Results:
- Chondrogenic differentiation of TD1 and ACH iPSCs resulted in degraded cartilage.
- Statin treatment corrected cartilage degradation in both TD1 and ACH iPSC models.
- Statin administration significantly improved bone growth in an ACH mouse model.
Conclusions:
- Statins demonstrate therapeutic potential for FGFR3-related skeletal dysplasias.
- Statin treatment can rescue cellular defects and promote bone growth in models of TD1 and ACH.
- Statins may offer a viable medical treatment for infants and children diagnosed with TD1 and ACH.
