ArticleHuman molecular genetics2011
A Phe377del mutation in ANK leads to impaired osteoblastogenesis and osteoclastogenesis in a mouse model for craniometaphyseal dysplasia (CMD).
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01630460 (Identification of Mutations That Lead to Craniometaphyseal Dysplasia in Families and Isolated Cases and Studies of Cellular and Molecular Mechanisms), which is not on this map. Cited by 30 papers.
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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.
Identification of Mutations That Lead to Craniometaphyseal Dysplasia in Families and Isolated Cases and Studies of Cellular and Molecular Mechanisms
Who cites it
30 citing papers in PubMed, 55 citations in OpenAlex.
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- Animal models of tendon calcification: Past, present, and future.Animal models and experimental medicine · 2024Review
- Hypophosphatemic rickets: An unexplained early feature of craniometaphyseal dysplasia.Bone reports · 2023Article
- Wnt/β-Catenin Signaling in Craniomaxillofacial Osteocytes.Current osteoporosis reports · 2023Review
- Special manifestations and treatment of rare cases of snoring with special facial features and hearing loss in children.The Journal of international medical research · 2022Article
- A three-year clinical investigation of a Chinese child with craniometaphyseal dysplasia caused by a mutatedWorld journal of clinical cases · 2021Article
- Differentiation of Human Induced Pluripotent Stem Cells (hiPSCs) into Osteoclasts.Bio-protocol · 2020Article
- Restriction of Dietary Phosphate Ameliorates Skeletal Abnormalities in a Mouse Model for Craniometaphyseal Dysplasia.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020Article
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- Alkaline Phosphatases Account for Low Plasma Levels of Inorganic Pyrophosphate in Chronic Kidney Disease.Frontiers in cell and developmental biology · 2020Article
- Molecular Control of Phosphorus Homeostasis and Precision Treatment of Hypophosphatemic Disorders.Current molecular biology reports · 2019Article
- Mandibular dysmorphology due to abnormal embryonic osteogenesis in FGFR2-related craniosynostosis mice.Disease models & mechanisms · 2019Article
- Rapid degradation of progressive ankylosis protein (ANKH) in craniometaphyseal dysplasia.Scientific reports · 2018Article
- Human Genetics of Sclerosing Bone Disorders.Current osteoporosis reports · 2018Review
- Biology of Fibroblast Growth Factor 23: From Physiology to Pathology.Cold Spring Harbor perspectives in medicine · 2018Review
- Craniometaphyseal Dysplasia Mutations in ANKH Negatively Affect Human Induced Pluripotent Stem Cell Differentiation into Osteoclasts.Stem cell reports · 2017Article
- Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies.Human genome variation · 2017Article
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5 authors at 1 institution in 1 country.
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Abstract
Craniometaphyseal dysplasia (CMD) is a rare genetic disorder with hyperostosis of craniofacial bones and widened metaphyses in long bones. Patients often suffer from neurological symptoms due to obstruction of cranial foramina. No proven treatment is available and the pathophysiology is largely unknown. A Phe377 (TTC(1130-1132)) deletion in exon 9 of the pyrophosphate (PPi) transporter ANK leads to CMD-like features in an Ank(KI/KI) mouse model. Here, we investigated the effects of CMD-mutant ANK on mineralization and bone mass at a cellular level. Ank(KI/KI) osteoblast cultures showed decreased mineral deposition. Expression of bone mineralization regulating genes Mmp13, Ocn, Osx and Phex was reduced in Ank(KI/KI) osteoblasts, while the Fgf23 mRNA level was highly elevated in Ank(KI/KI) calvarial and femoral bones. Since ANK is a known PPi transporter, we examined other regulators of Pi/PPi homeostasis Enpp1 and Tnap. Significantly increased ENPP1 activity may compensate for dysfunctional mutant ANK leading to comparable extracellular PPi levels in Ank(+/+) osteoblasts. Similar to Ank(KI/KI) bone marrow-derived macrophage cultures, peripheral blood cultures from CMD patients exhibited reduced osteoclastogenesis. Cell-autonomous effects in Ank(KI/KI) osteoclasts resulted in disrupted actin ring formation and cell fusion. In addition, Ank(KI/KI) osteoblasts failed to adequately support osteoclastogenesis. Increased bone mass could partially be rescued by bone marrow transplants supporting our hypothesis that reduced osteoclastogenesis contributes at least in part to hyperostosis. We conclude that the Phe377del mutation in ANK causes impaired osteoblastogenesis and osteoclastogenesis resulting in hypomineralization and a high bone mass phenotype.
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