ArticleStem cells and development2014
Patient-derived skeletal dysplasia induced pluripotent stem cells display abnormal chondrogenic marker expression and regulation by BMP2 and TGFβ1.
Article in Stem cells and development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Small molecule inhibition rescues the skeletal dysplasia phenotype of Trpv4 mutant mice.JCI insight · 2026Article
- Skeletal dysplasia-causing mutations in TRPV4 alter the chondrocyte transcriptomic response to mechanical loading.American journal of physiology. Cell physiology · 2025Article
- iPSCs chondrogenic differentiation for personalized regenerative medicine: a literature review.Stem cell research & therapy · 2024Review
- Clinical Potential of Cellular Material Sources in the Generation of iPSC-Based Products for the Regeneration of Articular Cartilage.International journal of molecular sciences · 2023Review
- Equine induced pluripotent stem cells are responsive to inflammatory cytokines before and after differentiation into musculoskeletal cell types.In vitro cellular & developmental biology. Animal · 2023Article
- Article
- Chondrogenic Differentiation of Human-Induced Pluripotent Stem Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Review
- Review
- Transient receptor potential vanilloid 4 as a regulator of induced pluripotent stem cell chondrogenesis.Stem cells (Dayton, Ohio) · 2021Article
- Impaired neurite development and mitochondrial dysfunction associated with calcium accumulation in dopaminergic neurons differentiated from the dental pulp stem cells of a patient with metatropic dysplasia.Biochemistry and biophysics reports · 2021Article
- Article
- Dental Pulp-Derived Mesenchymal Stem Cells for Modeling Genetic Disorders.International journal of molecular sciences · 2021Review
- Review
- Induced Pluripotent Stem Cell-Differentiated Chondrocytes Repair Cartilage Defect in a Rabbit Osteoarthritis Model.Stem cells international · 2020Article
- Novel gain-of-function mutation ofBiochemistry and biophysics reports · 2019Article
- HMGB1 promotes bone fracture healing through activation of ERK signaling pathway in a rat tibial fracture model.The Kaohsiung journal of medical sciences · 2019Article
- Protein informatics combined with multiple data sources enriches the clinical characterization of novel TRPV4 variant causing an intermediate skeletal dysplasia.Molecular genetics & genomic medicine · 2019Article
- CaMKII inhibition in human primary and pluripotent stem cell-derived chondrocytes modulates effects of TGFβ and BMP through SMAD signaling.Osteoarthritis and cartilage · 2019Article
- Mesenchymal Stem Cell Therapy for Bone Regeneration.Clinics in orthopedic surgery · 2018Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
Skeletal dysplasias (SDs) are caused by abnormal chondrogenesis during cartilage growth plate differentiation. To study early stages of aberrant cartilage formation in vitro, we generated the first induced pluripotent stem cells (iPSCs) from fibroblasts of an SD patient with a lethal form of metatropic dysplasia, caused by a dominant mutation (I604M) in the calcium channel gene TRPV4. When micromasses were grown in chondrogenic differentiation conditions and compared with control iPSCs, mutant TRPV4-iPSCs showed significantly (P<0.05) decreased expression by quantitative real-time polymerase chain reaction of COL2A1 (IIA and IIB forms), SOX9, Aggrecan, COL10A1, and RUNX2, all of which are cartilage growth plate markers. We found that stimulation with BMP2, but not TGFβ1, up-regulated COL2A1 (IIA and IIB) and SOX9 gene expression, only in control iPSCs. COL2A1 (Collagen II) expression data were confirmed at the protein level by western blot and immunofluorescence microscopy. TRPV4-iPSCs showed only focal areas of Alcian blue stain for proteoglycans, while in control iPSCs the stain was seen throughout the micromass sample. Similar staining patterns were found in neonatal cartilage from control and patient samples. We also found that COL1A1 (Collagen I), a marker of osteogenic differentiation, was significantly (P<0.05) up-regulated at the mRNA level in TRPV4-iPSCs when compared with the control, and confirmed at the protein level. Collagen I expression in the TRPV4 model also may correlate with abnormal staining patterns seen in patient tissues. This study demonstrates that an iPSC model can recapitulate normal chondrogenesis and that mutant TRPV4-iPSCs reflect molecular evidence of aberrant chondrogenic developmental processes, which could be used to design therapeutic approaches for disorders of cartilage.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.