| Autor: |
Hiroki Maruyama, Atsumi Taguchi, Mariko Mikame, Hongmei Lu, Norihiro Tada, Muneaki Ishijima, Haruka Kaneko, Mariko Kawai, Sawako Goto, Akihiko Saito, Riuko Ohashi, Yuji Nishikawa, Satoshi Ishii |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
FASEB BioAdvances, Vol 2, Iss 6, Pp 365-381 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2573-9832 |
| DOI: |
10.1096/fba.2019-00080 |
| Popis: |
Abstract Low bone mineral density (BMD)—diagnosed as osteoporosis or osteopenia—has been reported as a new characteristic feature of Fabry disease; however, the mechanism underlying the development of low BMD is unknown. We previously revealed that a mouse model of Fabry disease [GlatmTg(CAG‐A4GALT)] exhibits impaired functioning of medullary thick ascending limb (mTAL), leading to insufficient Ca2+ reabsorption and hypercalciuria. Here, we investigated bone metabolism in GlatmTg(CAG‐A4GALT) mice without marked glomerular or proximal tubular damage. Low BMD was detected by 20 weeks of age via micro‐X‐ray‐computed tomography. Bone histomorphometry revealed that low BMD results by accelerated bone resorption and osteomalacia. Plasma parathyroid hormone levels increased in response to low blood Ca2+—not plasma fibroblast growth factor 23 (FGF‐23) elevation—by 5 weeks of age and showed progressively increased phosphaturic action. Secondary hyperparathyroidism developed by 20 weeks of age and caused hyperphosphatemia, which increased plasma FGF‐23 levels with phosphaturic action. The expression of 1α‐hydroxylase [synthesis of 1α,25(OH)2D3] in the kidney did not decrease, but that of 24‐hydroxylase [degradation of 1α,25(OH)2D3] decreased. Vitamin D deficiency was ruled out as the cause of osteomalacia, as plasma 1α,25(OH)2D3 and 25(OH)D3 levels were maintained. Results demonstrate that secondary hyperparathyroidism due to mTAL impairment causes accelerated bone resorption and osteomalacia due to hyperphosphaturia and hypercalciuria, leading to low BMD in Fabry model mice. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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