Prevention of Hypomineralization In Auditory Ossicles of Vitamin D Receptor (Vdr) Deficient Mice
Intact mineralization of the auditory ossicles - the smallest bones in the body - is essential for sound transmission in the middle ear, while ossicular hypomineralization is associated with conductive hearing loss. Here, we performed a high-resolution analysis of the ossicles in vitamin D receptor...
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| Format: | Article |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.901265/full |
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| author | Maximilian M. Delsmann Maximilian M. Delsmann Jonathan Peichl Timur A. Yorgan Frank Timo Beil Michael Amling Marie B. Demay Tim Rolvien |
| author_facet | Maximilian M. Delsmann Maximilian M. Delsmann Jonathan Peichl Timur A. Yorgan Frank Timo Beil Michael Amling Marie B. Demay Tim Rolvien |
| author_sort | Maximilian M. Delsmann |
| collection | DOAJ |
| description | Intact mineralization of the auditory ossicles - the smallest bones in the body - is essential for sound transmission in the middle ear, while ossicular hypomineralization is associated with conductive hearing loss. Here, we performed a high-resolution analysis of the ossicles in vitamin D receptor deficient mice (Vdr-/-), which are characterized by hypocalcemia and skeletal mineralization defects, and investigated whether local hypomineralization can be prevented by feeding a calcium-rich rescue diet (Vdr-/- res). In Vdr-/- mice fed a regular diet (Vdr-/- reg), quantitative backscattered electron imaging (qBEI) revealed an increased void volume (porosity, p<0.0001) along with lower mean calcium content (CaMean, p=0.0008) and higher heterogeneity of mineralization (CaWidth, p=0.003) compared to WT mice. Furthermore, a higher osteoid volume per bone volume (OV/BV; p=0.0002) and a higher osteocyte lacunar area (Lc.Ar; p=0.01) were found in histomorphometric analysis in Vdr-/- reg mice. In Vdr-/- res mice, full rescue of OV/BV and Lc.Ar (both p>0.05 vs. WT) and partial rescue of porosity and CaWidth (p=0.02 and p=0.04 vs. WT) were observed. Compared with Hyp mice, a model of X-linked hypophosphatemic rickets, Vdr-/- reg mice showed a lower osteoid volume in the ossicles (p=0.0002), but similar values in the lumbar spine. These results are consistent with later postnatal impairment of mineral homeostasis in Vdr-/- mice than in Hyp mice, underscoring the importance of intact mineral homeostasis for ossicle mineralization during development. In conclusion, we revealed a distinct phenotype of hypomineralization in the auditory ossicles of Vdr-/- mice that can be partially prevented by a rescue diet. Since a positive effect of a calcium-rich diet on ossicular mineralization was demonstrated, our results open new treatment strategies for conductive hearing loss. Future studies should investigate the impact of improved ossicular mineralization on hearing function. |
| first_indexed | 2024-04-12T14:25:42Z |
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| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-12T14:25:42Z |
| publishDate | 2022-06-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-dd8910bc725d42c49340276b64b1d2db2022-12-22T03:29:26ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-06-011310.3389/fendo.2022.901265901265Prevention of Hypomineralization In Auditory Ossicles of Vitamin D Receptor (Vdr) Deficient MiceMaximilian M. Delsmann0Maximilian M. Delsmann1Jonathan Peichl2Timur A. Yorgan3Frank Timo Beil4Michael Amling5Marie B. Demay6Tim Rolvien7Department of Trauma and Orthopaedic Surgery, Division of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Osteology and Biomechanics, University Medical Center Hamburg Eppendorf, Hamburg, GermanyDepartment of Otorhinolaryngology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Osteology and Biomechanics, University Medical Center Hamburg Eppendorf, Hamburg, GermanyDepartment of Trauma and Orthopaedic Surgery, Division of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Osteology and Biomechanics, University Medical Center Hamburg Eppendorf, Hamburg, GermanyEndocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Trauma and Orthopaedic Surgery, Division of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyIntact mineralization of the auditory ossicles - the smallest bones in the body - is essential for sound transmission in the middle ear, while ossicular hypomineralization is associated with conductive hearing loss. Here, we performed a high-resolution analysis of the ossicles in vitamin D receptor deficient mice (Vdr-/-), which are characterized by hypocalcemia and skeletal mineralization defects, and investigated whether local hypomineralization can be prevented by feeding a calcium-rich rescue diet (Vdr-/- res). In Vdr-/- mice fed a regular diet (Vdr-/- reg), quantitative backscattered electron imaging (qBEI) revealed an increased void volume (porosity, p<0.0001) along with lower mean calcium content (CaMean, p=0.0008) and higher heterogeneity of mineralization (CaWidth, p=0.003) compared to WT mice. Furthermore, a higher osteoid volume per bone volume (OV/BV; p=0.0002) and a higher osteocyte lacunar area (Lc.Ar; p=0.01) were found in histomorphometric analysis in Vdr-/- reg mice. In Vdr-/- res mice, full rescue of OV/BV and Lc.Ar (both p>0.05 vs. WT) and partial rescue of porosity and CaWidth (p=0.02 and p=0.04 vs. WT) were observed. Compared with Hyp mice, a model of X-linked hypophosphatemic rickets, Vdr-/- reg mice showed a lower osteoid volume in the ossicles (p=0.0002), but similar values in the lumbar spine. These results are consistent with later postnatal impairment of mineral homeostasis in Vdr-/- mice than in Hyp mice, underscoring the importance of intact mineral homeostasis for ossicle mineralization during development. In conclusion, we revealed a distinct phenotype of hypomineralization in the auditory ossicles of Vdr-/- mice that can be partially prevented by a rescue diet. Since a positive effect of a calcium-rich diet on ossicular mineralization was demonstrated, our results open new treatment strategies for conductive hearing loss. Future studies should investigate the impact of improved ossicular mineralization on hearing function.https://www.frontiersin.org/articles/10.3389/fendo.2022.901265/fullvitamin D receptormineralizationqBEIauditory ossicleshearing |
| spellingShingle | Maximilian M. Delsmann Maximilian M. Delsmann Jonathan Peichl Timur A. Yorgan Frank Timo Beil Michael Amling Marie B. Demay Tim Rolvien Prevention of Hypomineralization In Auditory Ossicles of Vitamin D Receptor (Vdr) Deficient Mice Frontiers in Endocrinology vitamin D receptor mineralization qBEI auditory ossicles hearing |
| title | Prevention of Hypomineralization In Auditory Ossicles of Vitamin D Receptor (Vdr) Deficient Mice |
| title_full | Prevention of Hypomineralization In Auditory Ossicles of Vitamin D Receptor (Vdr) Deficient Mice |
| title_fullStr | Prevention of Hypomineralization In Auditory Ossicles of Vitamin D Receptor (Vdr) Deficient Mice |
| title_full_unstemmed | Prevention of Hypomineralization In Auditory Ossicles of Vitamin D Receptor (Vdr) Deficient Mice |
| title_short | Prevention of Hypomineralization In Auditory Ossicles of Vitamin D Receptor (Vdr) Deficient Mice |
| title_sort | prevention of hypomineralization in auditory ossicles of vitamin d receptor vdr deficient mice |
| topic | vitamin D receptor mineralization qBEI auditory ossicles hearing |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.901265/full |
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