Loss of ninein interferes with osteoclast formation and causes premature ossification
- University Toulouse III, CNRS, France
- University Toulouse III / CNRS, France
- Université de Toulouse, CNRS, UPS, France
Abstract
Ninein is a centrosome protein that has been implicated in microtubule anchorage and centrosome cohesion. Mutations in the human NINEIN gene have been linked to Seckel syndrome and to a rare form of skeletal dysplasia. However, the role of ninein in skeletal development remains unknown. Here, we describe a ninein knockout mouse with advanced endochondral ossification during embryonic development. Although the long bones maintain a regular size, the absence of ninein delays the formation of the bone marrow cavity in the prenatal tibia. Likewise, intramembranous ossification in the skull is more developed, leading to a premature closure of the interfrontal suture. We demonstrate that ninein is strongly expressed in osteoclasts of control mice, and that its absence reduces the fusion of precursor cells into syncytial osteoclasts, whereas the number of osteoblasts remains unaffected. As a consequence, ninein-deficient osteoclasts have a reduced capacity to resorb bone. At the cellular level, the absence of ninein interferes with centrosomal microtubule organization, reduces centrosome cohesion, and provokes the loss of centrosome clustering in multinucleated mature osteoclasts. We propose that centrosomal ninein is important for osteoclast fusion, to enable a functional balance between bone-forming osteoblasts and bone-resorbing osteoclasts during skeletal development.
Data availability
10.6084/m9.figshare.25650942source data files have been provided for Figure 7-figure supplement 1
Article and author information
Author details
Funding
Agence Nationale de la Recherche (ANR16-CE13-0005-01)
- Christel Vérollet
Universite Toulouse III (financement S&N Bernard)
- Andreas Merdes
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Mei Wan, Johns Hopkins University, United States
Ethics
Animal experimentation: All animal experiments were approved by the Institutional Animal Care and Use Committee at the Genotoul Anexplo facilities of the Center for Integrative Biology, University Toulouse III (institution agreement #D3155511, project agreement APAFIS#2725-2015111213203624 v5).
Version history
- Received: October 11, 2023
- Preprint posted: November 6, 2023 (view preprint)
- Accepted: June 4, 2024
- Accepted Manuscript published: June 5, 2024 (version 1)
- Version of Record published: June 13, 2024 (version 2)
Copyright
© 2024, Gilbert et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Loss of ninein interferes with osteoclast formation and causes premature ossification
eLife 13:e93457.
https://doi.org/10.7554/eLife.93457
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