ArticleHuman molecular genetics2018
Gaucher disease iPSC-derived osteoblasts have developmental and lysosomal defects that impair bone matrix deposition.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 48 citations in OpenAlex.
- New insights into bone pathology through a transcriptomic profiling of an osteoblast model of Gaucher disease.Molecular genetics and metabolism reports · 2026Article
- Improvement of Bone Mineral Density in Patients with Type 1 Gaucher Disease Treated with Velaglucerase Alfa: Results from Clinical Studies.Journal of clinical medicine · 2026Article
- The global impact of imiglucerase therapy in children with Gaucher disease types 1 and 3: a real-world analysis from the International Collaborative Gaucher Group Gaucher Registry.Orphanet journal of rare diseases · 2026Article
- Refining Mouse Models of Gaucher Disease: Advancing Mechanistic Insights, Biomarker Discovery, and Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Inhibition or genetic reduction of ASAH1/acid ceramidase restore α-synuclein clearance in mutant GBA1 dopamine neurons from Parkinson's patients.Human molecular genetics · 2025Article
- Gaucher disease, state of the art and perspectives.Journal of internal medicine · 2025Review
- Current opinion on pluripotent stem cell technology in Gaucher's disease: challenges and future prospects.Cytotechnology · 2025Review
- The Diagnosis and Therapy of Osteoporosis in Gaucher Disease.Calcified tissue international · 2025Review
- Age-related inflammatory biomarkers in early-onset osteoporosis in females with Gaucher disease.Frontiers in endocrinology · 2025Article
- High-throughput screening for small-molecule stabilizers of misfolded glucocerebrosidase in Gaucher disease and Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Development of quantitative high-throughput screening assays to identify, validate, and optimize small-molecule stabilizers of misfolded β-glucocerebrosidase with therapeutic potential for Gaucher disease and Parkinson's disease.bioRxiv : the preprint server for biology · 2024Article
- Biofabrication of anBiofabrication · 2023Article
- Bone marrow adipocytes alteration in anMolecular genetics and metabolism reports · 2023Article
- Exploring the Pathophysiologic Cascade Leading to Osteoclastogenic Activation in Gaucher Disease Monocytes Generated via CRISPR/Cas9 Technology.International journal of molecular sciences · 2023Article
- Article
- Acid ceramidase involved in pathogenic cascade leading to accumulation of α-synuclein in iPSC model of GBA1-associated Parkinson's disease.Human molecular genetics · 2023Article
- A Highly Selective GSK-3β Inhibitor CHIR99021 Promotes Osteogenesis by Activating Canonical and Autophagy-Mediated Wnt Signaling.Frontiers in endocrinology · 2022Article
- Wnt signaling pathway inhibitors, sclerostin and DKK-1, correlate with pain and bone pathology in patients with Gaucher disease.Frontiers in endocrinology · 2022Article
- Neuronopathic Gaucher disease: Beyond lysosomal dysfunction.Frontiers in molecular neuroscience · 2022Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Gaucher disease (GD) is caused by bi-allelic mutations in GBA1, the gene that encodes acid β-glucocerebrosidase (GCase). Individuals affected by GD have hematologic, visceral and bone abnormalities, and in severe cases there is also neurodegeneration. To shed light on the mechanisms by which mutant GBA1 causes bone disease, we examined the ability of human induced pluripotent stem cells (iPSC) derived from patients with Types 1, 2 and 3 GD, to differentiate to osteoblasts and carry out bone deposition. Differentiation of GD iPSC to osteoblasts revealed that these cells had developmental defects and lysosomal abnormalities that interfered with bone matrix deposition. Compared with controls, GD iPSC-derived osteoblasts exhibited reduced expression of osteoblast differentiation markers, and bone matrix protein and mineral deposition were defective. Concomitantly, canonical Wnt/β catenin signaling in the mutant osteoblasts was downregulated, whereas pharmacological Wnt activation with the GSK3β inhibitor CHIR99021 rescued GD osteoblast differentiation and bone matrix deposition. Importantly, incubation with recombinant GCase (rGCase) rescued the differentiation and bone-forming ability of GD osteoblasts, demonstrating that the abnormal GD phenotype was caused by GCase deficiency. GD osteoblasts were also defective in their ability to carry out Ca2+-dependent exocytosis, a lysosomal function that is necessary for bone matrix deposition. We conclude that normal GCase enzymatic activity is required for the differentiation and bone-forming activity of osteoblasts. Furthermore, the rescue of bone matrix deposition by pharmacological activation of Wnt/β catenin in GD osteoblasts uncovers a new therapeutic target for the treatment of bone abnormalities in GD.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.