Loss of ninein interferes with osteoclast formation and causes premature ossification.

Autor:	Gilbert T; Molecular, Cellular and Developmental Biology, Centre de Biologie Intégrative, UMR5077, CNRS & Université Paul Sabatier, Toulouse, France., Gorlt C; Molecular, Cellular and Developmental Biology, Centre de Biologie Intégrative, UMR5077, CNRS & Université Paul Sabatier, Toulouse, France.; Institut de Pharmacologie et de Biologie Structurale, UMR5089, CNRS & Université Paul Sabatier, Toulouse, France., Barbier M; Molecular, Cellular and Developmental Biology, Centre de Biologie Intégrative, UMR5077, CNRS & Université Paul Sabatier, Toulouse, France., Duployer B; CIRIMAT, UMR5085, CNRS & Université Paul Sabatier, Toulouse, France., Plozza M; Institut de Pharmacologie et de Biologie Structurale, UMR5089, CNRS & Université Paul Sabatier, Toulouse, France., Dufrancais O; Institut de Pharmacologie et de Biologie Structurale, UMR5089, CNRS & Université Paul Sabatier, Toulouse, France., Martet LE; Molecular, Cellular and Developmental Biology, Centre de Biologie Intégrative, UMR5077, CNRS & Université Paul Sabatier, Toulouse, France., Dalbard E; Molecular, Cellular and Developmental Biology, Centre de Biologie Intégrative, UMR5077, CNRS & Université Paul Sabatier, Toulouse, France., Segot L; Molecular, Cellular and Developmental Biology, Centre de Biologie Intégrative, UMR5077, CNRS & Université Paul Sabatier, Toulouse, France., Tenailleau C; CIRIMAT, UMR5085, CNRS & Université Paul Sabatier, Toulouse, France., Haren L; Molecular, Cellular and Developmental Biology, Centre de Biologie Intégrative, UMR5077, CNRS & Université Paul Sabatier, Toulouse, France., Vérollet C; Institut de Pharmacologie et de Biologie Structurale, UMR5089, CNRS & Université Paul Sabatier, Toulouse, France.; International Research Project CNRS 'MAC-TB/HIV', Toulouse, France., Bierkamp C; Molecular, Cellular and Developmental Biology, Centre de Biologie Intégrative, UMR5077, CNRS & Université Paul Sabatier, Toulouse, France., Merdes A; Molecular, Cellular and Developmental Biology, Centre de Biologie Intégrative, UMR5077, CNRS & Université Paul Sabatier, Toulouse, France.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2024 Jun 05; Vol. 13. Date of Electronic Publication: 2024 Jun 05.
DOI:	10.7554/eLife.93457
Abstrakt:	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. Competing Interests: TG, CG, MB, BD, MP, OD, LM, ED, LS, CT, LH, CV, CB, AM No competing interests declared (© 2024, Gilbert et al.)
Databáze:	MEDLINE
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