ArticlePLoS genetics2011
The abnormal phenotypes of cartilage and bone in calcium-sensing receptor deficient mice are dependent on the actions of calcium, phosphorus, and PTH.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Biased agonism of G protein-coupled receptors as a novel strategy for osteoarthritis therapy.Bone research · 2025Review
- A Sonic Hedgehog-Gli-Bmi1 signaling pathway plays a critical role in p27 deficiency induced bone anabolism.International journal of biological sciences · 2022Article
- SIRT1/FOXO3a axis plays an important role in the prevention of mandibular bone loss induced by 1,25(OH)International journal of biological sciences · 2020Article
- 1,25-Dihydroxyvitamin D insufficiency accelerates age-related bone loss by increasing oxidative stress and cell senescence.American journal of translational research · 2020Article
- The Nervous System Relevance of the Calcium Sensing Receptor in Health and Disease.Molecules (Basel, Switzerland) · 2019Review
- Evolution of Our Understanding of the Hyperparathyroid Syndromes: A Historical Perspective.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Review
- DNA damage checkpoint pathway modulates the regulation of skeletal growth and osteoblastic bone formation by parathyroid hormone-related peptide.International journal of biological sciences · 2018Article
- Specific ablation of mouse Fam20C in cells expressing type I collagen leads to skeletal defects and hypophosphatemia.Scientific reports · 2017Article
- Atypical skeletal manifestations of rickets in a familial hypocalciuric hypercalcemia patient.Bone research · 2017Article
- The calcium-sensing receptor in bone metabolism: from bench to bedside and back.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2015Review
- The calcium-sensing receptor in bone--mechanistic and therapeutic insights.Nature reviews. Endocrinology · 2015Review
- Recombinant human parathyroid hormone related protein 1-34 and 1-84 and their roles in osteoporosis treatment.PloS one · 2014Article
- Calcium sensing receptor absence delays postnatal brain development via direct and indirect mechanisms.Molecular neurobiology · 2013Article
- Neonatal seizures: controversies and challenges in translating new therapies from the lab to the isolette.The European journal of neuroscience · 2012Review
- Parathyroid diseases and animal models.Frontiers in endocrinology · 2012Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Patients with neonatal severe hyperparathyroidism (NSHPT) are homozygous for the calcium-sensing receptor (CaR) mutation and have very high circulating PTH, abundant parathyroid hyperplasia, and severe life-threatening hypercalcemia. Mice with homozygous deletion of CaR mimic the syndrome of NSHPT. To determine effects of CaR deficiency on skeletal development and interactions between CaR and 1,25(OH)(2)D(3) or PTH on calcium and skeletal homeostasis, we compared the skeletal phenotypes of homozygous CaR-deficient (CaR(-/-)) mice to those of double homozygous CaR- and 1α(OH)ase-deficient [CaR(-/-)1α(OH)ase(-/-)] mice or those of double homozygous CaR- and PTH-deficient [CaR(-/-)PTH(-/-)] mice at 2 weeks of age. Compared to wild-type littermates, CaR(-/-) mice had hypercalcemia, hypophosphatemia, hyperparathyroidism, and severe skeletal growth retardation. Chondrocyte proliferation and PTHrP expression in growth plates were reduced significantly, whereas trabecular volume, osteoblast number, osteocalcin-positive areas, expression of the ALP, type I collagen, osteocalcin genes, and serum ALP levels were increased significantly. Deletion of 1α(OH)ase in CaR(-/-) mice resulted in a longer lifespan, normocalcemia, lower serum phosphorus, greater elevation in PTH, slight improvement in skeletal growth with increased chondrocyte proliferation and PTHrP expression, and further increases in indices of osteoblastic bone formation. Deletion of PTH in CaR(-/-) mice resulted in rescue of early lethality, normocalcemia, increased serum phosphorus, undetectable serum PTH, normalization in skeletal growth with normal chondrocyte proliferation and enhanced PTHrP expression, and dramatic decreases in indices of osteoblastic bone formation. Our results indicate that reductions in hypercalcemia play a critical role in preventing the early lethality of CaR(-/-) mice and that defects in endochondral bone formation in CaR(-/-) mice result from effects of the marked elevation in serum calcium concentration and the decreases in serum phosphorus concentration and skeletal PTHrP levels, whereas the increased osteoblastic bone formation results from direct effects of PTH.
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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.