Theoretical evidence of osteoblast self-inhibition after activation of the genetic regulatory network controlling mineralization

Abdennasser Chekroun; Laurent Pujo-Menjouet; Steve Falcoz; Kamyine Tsuen; Kevin Yueh-Hsun Yang; Jean-Philippe Berteau

doi:10.1016/j.jtbi.2022.111005

Theoretical evidence of osteoblast self-inhibition after activation of the genetic regulatory network controlling mineralization

J Theor Biol. 2022 Mar 21;537:111005. doi: 10.1016/j.jtbi.2022.111005. Epub 2022 Jan 12.

Authors

Abdennasser Chekroun¹, Laurent Pujo-Menjouet², Steve Falcoz³, Kamyine Tsuen⁴, Kevin Yueh-Hsun Yang⁵, Jean-Philippe Berteau⁶

Affiliations

¹ Laboratoire d'Analyse Non Linéaire et Mathématiques Appliquées, University of Tlemcen, Chetouane 13000, Algeria; Univ Lyon, Inria, Université Claude Bernard Lyon 1, CNRS UMR5208, Institut Camille Jordan, F-69603 Villeurbanne, France.
² Univ Lyon, Inria, Université Claude Bernard Lyon 1, CNRS UMR5208, Institut Camille Jordan, F-69603 Villeurbanne, France. Electronic address: pujo@math.univ-lyon1.fr.
³ Univ Lyon, Inria, Université Claude Bernard Lyon 1, CNRS UMR5208, Institut Camille Jordan, F-69603 Villeurbanne, France; Department of Physical Therapy, College of Staten Island, City University of New York, New York, NY 10314, USA.
⁴ Department of Physical Therapy, College of Staten Island, City University of New York, New York, NY 10314, USA; Nanoscience Initiative, Advance Science Research Center, City University of New York, New York, NY 10031, USA.
⁵ New York Center for Biomedical Engineering, City College of New York, City University of New York, New York, NY 10031, USA.
⁶ Department of Physical Therapy, College of Staten Island, City University of New York, New York, NY 10314, USA; New York Center for Biomedical Engineering, City College of New York, City University of New York, New York, NY 10031, USA; Nanoscience Initiative, Advance Science Research Center, City University of New York, New York, NY 10031, USA.

PMID: 35031309
DOI: 10.1016/j.jtbi.2022.111005

Abstract

Bone is a hard-soft biomaterial built through a self-assembly process under genetic regulatory network (GRN) monitoring. This paper aims to capture the behavior of the bone GRN part that controls mineralization by using a mathematical model. Here, we provide an advanced review of empirical evidence about interactions between gene coding (i) transcription factors and (ii) bone proteins. These interactions are modeled with nonlinear differential equations using Michaelis-Menten and Hill functions. Compared to empirical evidence - coming from osteoblasts culture -, the two best systems (among 12⁶=2,985,984 possibilities) use factors of inhibition from the start of the activation of each gene. It reveals negative indirect interactions coming from either negative feedback loops or the recently depicted micro-RNAs. The difference between the two systems also lies in the BSP equation and two ways for activating and reducing its production. Thus, it highlights the critical role of BSP in the bone GRN that acts on bone mineralization. Our study provides the first theoretical evidence of osteoblast self-inhibition after activation of the genetic regulatory network controlling mineralization with this work.

Keywords: Bone; Genetic network; Hill functions; Nonlinear differential equations.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Calcification, Physiologic / genetics
Cell Differentiation
Gene Expression Regulation*
Gene Regulatory Networks*
Osteoblasts
Transcription Factors / metabolism

Substances

Transcription Factors