RRC ID 69960
Author Nagashima T, Ninomiya T, Nakamura Y, Nishimura S, Ohashi A, Aoki J, Mizoguchi T, Tonogi M, Takahashi T.
Title p53 deficiency promotes bone regeneration by functional regulation of mesenchymal stromal cells and osteoblasts.
Journal J Bone Miner Metab
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.
Volume 40(3)
Pages 434-447
Published 2022-5-1
DOI 10.1007/s00774-022-01314-w
PII 10.1007/s00774-022-01314-w
PMID 35195777
MeSH Animals Bone Regeneration* / physiology Cell Differentiation Core Binding Factor Alpha 1 Subunit* / genetics Core Binding Factor Alpha 1 Subunit* / metabolism Mesenchymal Stem Cells* / cytology Mesenchymal Stem Cells* / metabolism Mice Mice, Knockout Osteoblasts* / cytology Osteoblasts* / metabolism Osteogenesis Tumor Suppressor Protein p53* / deficiency Tumor Suppressor Protein p53* / genetics Tumor Suppressor Protein p53* / metabolism
IF 2.297
Mice RBRC01361