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Skeletal mineralization: mechanisms and diseases
Skeletal mineralization is initiated in matrix vesicles (MVs), the small extracellular vesicles derived from osteoblasts and chondrocytes. Calcium and inorganic phosphate (Pi) taken up by MVs form hydroxyapatite crystals, which propagate on collagen fibrils to mineralize the extracellular matrix. In...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Korean Society of Pediatric Endocrinology
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944863/ https://www.ncbi.nlm.nih.gov/pubmed/31905439 http://dx.doi.org/10.6065/apem.2019.24.4.213 |
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author | Michigami, Toshimi |
author_facet | Michigami, Toshimi |
author_sort | Michigami, Toshimi |
collection | PubMed |
description | Skeletal mineralization is initiated in matrix vesicles (MVs), the small extracellular vesicles derived from osteoblasts and chondrocytes. Calcium and inorganic phosphate (Pi) taken up by MVs form hydroxyapatite crystals, which propagate on collagen fibrils to mineralize the extracellular matrix. Insufficient calcium or phosphate impairs skeletal mineralization. Because active vitamin D is necessary for intestinal calcium absorption, vitamin D deficiency is a significant cause of rickets/osteomalacia. Chronic hypophosphatemia also results in rickets/osteomalacia. Excessive action of fibroblast growth factor 23 (FGF23), a key regulator of Pi metabolism, leads to renal Pi wasting and impairs vitamin D activation. X-linked hypophosphatemic rickets (XLH) is the most common form of hereditary FGF23-related hypophosphatemia, and enhanced FGF receptor (FGFR) signaling in osteocytes may be involved in the pathogenesis of this disease. Increased extracellular Pi triggers signal transduction via FGFR to regulate gene expression, implying a close relationship between Pi metabolism and FGFR. An anti-FGF23 antibody, burosumab, has recently been developed as a new treatment for XLH. In addition to various forms of rickets/osteomalacia, hypophosphatasia (HPP) is characterized by impaired skeletal mineralization. HPP is caused by inactivating mutations in tissue-nonspecific alkaline phosphatase, an enzyme rich in MVs. The recent development of enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase has improved the prognosis, motor function, and quality of life in patients with HPP. This links impaired skeletal mineralization with various conditions, and unraveling its pathogenesis will lead to more precise diagnoses and effective treatments. |
format | Online Article Text |
id | pubmed-6944863 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Korean Society of Pediatric Endocrinology |
record_format | MEDLINE/PubMed |
spelling | pubmed-69448632020-01-09 Skeletal mineralization: mechanisms and diseases Michigami, Toshimi Ann Pediatr Endocrinol Metab Review Article Skeletal mineralization is initiated in matrix vesicles (MVs), the small extracellular vesicles derived from osteoblasts and chondrocytes. Calcium and inorganic phosphate (Pi) taken up by MVs form hydroxyapatite crystals, which propagate on collagen fibrils to mineralize the extracellular matrix. Insufficient calcium or phosphate impairs skeletal mineralization. Because active vitamin D is necessary for intestinal calcium absorption, vitamin D deficiency is a significant cause of rickets/osteomalacia. Chronic hypophosphatemia also results in rickets/osteomalacia. Excessive action of fibroblast growth factor 23 (FGF23), a key regulator of Pi metabolism, leads to renal Pi wasting and impairs vitamin D activation. X-linked hypophosphatemic rickets (XLH) is the most common form of hereditary FGF23-related hypophosphatemia, and enhanced FGF receptor (FGFR) signaling in osteocytes may be involved in the pathogenesis of this disease. Increased extracellular Pi triggers signal transduction via FGFR to regulate gene expression, implying a close relationship between Pi metabolism and FGFR. An anti-FGF23 antibody, burosumab, has recently been developed as a new treatment for XLH. In addition to various forms of rickets/osteomalacia, hypophosphatasia (HPP) is characterized by impaired skeletal mineralization. HPP is caused by inactivating mutations in tissue-nonspecific alkaline phosphatase, an enzyme rich in MVs. The recent development of enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase has improved the prognosis, motor function, and quality of life in patients with HPP. This links impaired skeletal mineralization with various conditions, and unraveling its pathogenesis will lead to more precise diagnoses and effective treatments. Korean Society of Pediatric Endocrinology 2019-12 2019-12-31 /pmc/articles/PMC6944863/ /pubmed/31905439 http://dx.doi.org/10.6065/apem.2019.24.4.213 Text en © 2019 Annals of Pediatric Endocrinology & Metabolism This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Michigami, Toshimi Skeletal mineralization: mechanisms and diseases |
title | Skeletal mineralization: mechanisms and diseases |
title_full | Skeletal mineralization: mechanisms and diseases |
title_fullStr | Skeletal mineralization: mechanisms and diseases |
title_full_unstemmed | Skeletal mineralization: mechanisms and diseases |
title_short | Skeletal mineralization: mechanisms and diseases |
title_sort | skeletal mineralization: mechanisms and diseases |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944863/ https://www.ncbi.nlm.nih.gov/pubmed/31905439 http://dx.doi.org/10.6065/apem.2019.24.4.213 |
work_keys_str_mv | AT michigamitoshimi skeletalmineralizationmechanismsanddiseases |