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Erschienen in:

23.02.2022 | Original Article

p53 deficiency promotes bone regeneration by functional regulation of mesenchymal stromal cells and osteoblasts

verfasst von: Toshimichi Nagashima, Tadashi Ninomiya, Yoshiki Nakamura, Shirabe Nishimura, Akiko Ohashi, Junya Aoki, Toshihide Mizoguchi, Morio Tonogi, Tomihisa Takahashi

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 3/2022

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Abstract

Introduction

The detailed mechanism of the process during bone healing of drill-hole injury has been elucidated, but a crucial factor in regulating drill-hole healing has not been identified. The transcription factor p53 suppresses osteoblast differentiation through inhibition of osterix expression. In present study, we demonstrate the effects of p53 deficiency on the capacity of MSCs and osteoblasts during drill-hole healing.

Materials and methods

Mesenchymal stromal cells (MSCs) and osteoblasts were collected from bone marrow and calvaria of p53 knockout (KO) mice, respectively. The activities of cell mobility, cell proliferation, osteoblast differentiation, and wound healing of MSCs and/or osteoblasts were determined by in vitro experiments. In addition, bone healing of drill-hole injury in KO mice was examined by micro-CT and immunohistological analysis using anti-osterix, Runx2, and sclerostin antibodies.

Results

KO MSCs stimulated cell mobility, cell proliferation, and osteoblast differentiation. Likewise, KO osteoblasts enhanced cell proliferation and wound healing. KO MSCs and osteoblasts showed high potency in the inflammation and callus formation phases compared to those from wild-type (WT) mice. In addition, increased expression of osterix and Runx2 was observed in KO MSCs and osteoblasts that migrated in the drill-hole. Conversely, sclerostin expression was inhibited in KO mice. Eventually, KO mice exhibited high repairability of drill-hole injury, suggesting a novel role of p53 in MSCs and osteoblasts in improving bone healing.

Conclusion

p53 Deficiency promotes bone healing of drill-hole injury by enhancing the bone-regenerative ability of MSCs and osteoblasts.

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Titel: p53 deficiency promotes bone regeneration by functional regulation of mesenchymal stromal cells and osteoblasts
verfasst von: Toshimichi Nagashima
Tadashi Ninomiya
Yoshiki Nakamura
Shirabe Nishimura
Akiko Ohashi
Junya Aoki
Toshihide Mizoguchi
Morio Tonogi
Tomihisa Takahashi
Publikationsdatum: 23.02.2022
Verlag: Springer Nature Singapore
Erschienen in: Journal of Bone and Mineral Metabolism / Ausgabe 3/2022
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-022-01314-w

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p53 deficiency promotes bone regeneration by functional regulation of mesenchymal stromal cells and osteoblasts