دورية أكاديمية
أعرض في EDS

Impaired 1,25 dihydroxyvitamin D3 action and hypophosphatemia underlie the altered lacuno-canalicular remodeling observed in the Hyp mouse model of XLH.

التفاصيل البيبلوغرافية
العنوان: Impaired 1,25 dihydroxyvitamin D3 action and hypophosphatemia underlie the altered lacuno-canalicular remodeling observed in the Hyp mouse model of XLH.
المؤلفون: Yuan Y; Harvard Medical School, Boston, Massachusetts, United States of America.; Division of Endocrinology, Diabetes, Hypertension, Brigham and Women's Hospital, Boston, Massachusetts, United States of America., Jagga S; Harvard Medical School, Boston, Massachusetts, United States of America.; Division of Endocrinology, Diabetes, Hypertension, Brigham and Women's Hospital, Boston, Massachusetts, United States of America., Martins JS; Harvard Medical School, Boston, Massachusetts, United States of America.; Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America., Rana R; Division of Endocrinology, Diabetes, Hypertension, Brigham and Women's Hospital, Boston, Massachusetts, United States of America., Pajevic PD; Department of Translational Dental Medicine, Boston University School of Dental Medicine, Boston, Massachusetts, United States of America., Liu ES; Harvard Medical School, Boston, Massachusetts, United States of America.; Division of Endocrinology, Diabetes, Hypertension, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
المصدر: PloS one [PLoS One] 2021 May 27; Vol. 16 (5), pp. e0252348. Date of Electronic Publication: 2021 May 27 (Print Publication: 2021).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Bone Remodeling* , Osteocytes*/metabolism , Osteocytes*/pathology, Calcitriol/*deficiency , Familial Hypophosphatemic Rickets/*metabolism , Vitamin D Deficiency/*metabolism, Animals ; Cell Line ; Disease Models, Animal ; Female ; Fibroblast Growth Factor-23 ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout
مستخلص: Osteocytes remodel the perilacunar matrix and canaliculi. X-linked hypophosphatemia (XLH) is characterized by elevated serum levels of fibroblast growth factor 23 (FGF23), leading to decreased 1,25 dihydroxyvitamin D3 (1,25D) production and hypophosphatemia. Bones from mice with XLH (Hyp) have enlarged osteocyte lacunae, enhanced osteocyte expression of genes of bone remodeling, and impaired canalicular structure. The altered lacuno-canalicular (LCN) phenotype is improved with 1,25D or anti-FGF23 antibody treatment, pointing to roles for 1,25D and/or phosphate in regulating this process. To address whether impaired 1,25D action results in LCN alterations, the LCN phenotype was characterized in mice lacking the vitamin D receptor (VDR) in osteocytes (VDRf/f;DMP1Cre+). Mice lacking the sodium phosphate transporter NPT2a (NPT2aKO) have hypophosphatemia and high serum 1,25D levels, therefore the LCN phenotype was characterized in these mice to determine if increased 1,25D compensates for hypophosphatemia in regulating LCN remodeling. Unlike Hyp mice, neither VDRf/f;DMP1Cre+ nor NPT2aKO mice have dramatic alterations in cortical microarchitecture, allowing for dissecting 1,25D and phosphate specific effects on LCN remodeling in tibial cortices. Histomorphometric analyses demonstrate that, like Hyp mice, tibiae and calvariae in VDRf/f;DMP1Cre+ and NPT2aKO mice have enlarged osteocyte lacunae (tibiae: 0.15±0.02μm2(VDRf/f;DMP1Cre-) vs 0.19±0.02μm2(VDRf/f;DMP1Cre+), 0.12±0.02μm2(WT) vs 0.18±0.0μm2(NPT2aKO), calvariae: 0.09±0.02μm2(VDRf/f;DMP1Cre-) vs 0.11±0.02μm2(VDRf/f;DMP1Cre+), 0.08±0.02μm2(WT) vs 0.13±0.02μm2(NPT2aKO), p<0.05 all comparisons) and increased immunoreactivity of bone resorption marker Cathepsin K (Ctsk). The osteocyte enriched RNA isolated from tibiae in VDRf/f;DMP1Cre+ and NPT2aKO mice have enhanced expression of matrix resorption genes that are classically expressed by osteoclasts (Ctsk, Acp5, Atp6v0d2, Nhedc2). Treatment of Ocy454 osteocytes with 1,25D or phosphate inhibits the expression of these genes. Like Hyp mice, VDRf/f;DMP1Cre+ and NPT2aKO mice have impaired canalicular organization in tibia and calvaria. These studies demonstrate that hypophosphatemia and osteocyte-specific 1,25D actions regulate LCN remodeling. Impaired 1,25D action and low phosphate levels contribute to the abnormal LCN phenotype observed in XLH.
Competing Interests: The authors have declared that no competing interests exist.
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معلومات مُعتمدة: K08 AR067854 United States AR NIAMS NIH HHS; R01 AR076973 United States AR NIAMS NIH HHS; R03 AR073899 United States AR NIAMS NIH HHS
المشرفين على المادة: 0 (Fgf23 protein, mouse)
7Q7P4S7RRE (Fibroblast Growth Factor-23)
FXC9231JVH (Calcitriol)
تواريخ الأحداث: Date Created: 20210527 Date Completed: 20211022 Latest Revision: 20230504
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8158930
DOI: 10.1371/journal.pone.0252348
PMID: 34043707
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0252348