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

Toshimichi Nagashima1,2, Tadashi Ninomiya3,4, Yoshiki Nakamura1,5

  • 1Division of Oral Structural and Functional Biology, Nihon University Graduate School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan.

Journal of Bone and Mineral Metabolism
|February 23, 2022
PubMed
Abstract

Insights

p53 deficiency enhances bone healing by boosting mesenchymal stromal cells (MSCs) and osteoblasts. This study reveals p53

Area of Science:

  • Molecular Biology
  • Regenerative Medicine
  • Orthopedics

Background:

  • The precise mechanisms of bone healing after drill-hole injury are understood, yet key regulatory factors remain elusive.
  • The transcription factor p53 is known to inhibit osteoblast differentiation by suppressing osterix expression.

Purpose of the Study:

  • To investigate the impact of p53 deficiency on mesenchymal stromal cells (MSCs) and osteoblasts during drill-hole bone healing.
  • To elucidate the role of p53 in regulating the regenerative capacity of MSCs and osteoblasts for improved bone repair.

Main Methods:

  • Collected MSCs and osteoblasts from p53 knockout (KO) and wild-type (WT) mice.
  • Assessed cell mobility, proliferation, and osteoblast differentiation in vitro.
  • Evaluated drill-hole bone healing in KO mice using micro-CT and immunohistochemistry (osterix, Runx2, sclerostin).

Main Results:

  • p53-deficient MSCs and osteoblasts exhibited enhanced cell mobility, proliferation, differentiation, and wound healing.
  • KO cells demonstrated superior performance in inflammation and callus formation phases compared to WT.
  • Increased osterix and Runx2 expression, with decreased sclerostin, was observed in KO cells, correlating with improved bone repair.

Conclusions:

  • p53 deficiency significantly promotes bone healing in drill-hole injuries.
  • This promotion is achieved by enhancing the intrinsic bone-regenerative capabilities of MSCs and osteoblasts.
Keywords:
Drill-hole healingMesenchymal stromal cellsOsteoblastsSclerostinp53 deficiency

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