AUTHOR=Varadinkova S. , Oralova V. , Clarke M. , Frampton J. , Knopfova L. , Lesot H. , Bartos P. , Matalova E. 

TITLE=Expression dynamics of metalloproteinases during mandibular bone formation: association with Myb transcription factor

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2023.1168866

DOI=10.3389/fcell.2023.1168866

ISSN=2296-634X

ABSTRACT=<p>As the dentition forms and becomes functional, the alveolar bone is remodelled. Metalloproteinases are known to contribute to this process, but new regulators are emerging and their contextualization is challenging. This applies to Myb, a transcription factor recently reported to be involved in bone development and regeneration. The regulatory effect of Myb on <italic>Mmps</italic> expression has mostly been investigated in tumorigenesis, where Myb impacted the expression of <italic>Mmp1</italic>, <italic>Mmp2</italic>, <italic>Mmp7</italic>, and <italic>Mmp9</italic>. The aim of this investigation was to evaluate the regulatory influence of the Myb on <italic>Mmps</italic> gene expression, impacting osteogenesis and mandibular bone formation. For that purpose, knock-out mouse model was used. Gene expression of bone-related <italic>Mmps</italic> and the key osteoblastic transcription factors Runx2 and Sp7 was analysed in Myb knock-out mice mandibles at the survival limit. Out of the metalloproteinases under study, Mmp13 was significantly downregulated. The impact of Myb on the expression of <italic>Mmp13</italic> was confirmed by the overexpression of Myb in calvarial-derived cells causing upregulation of <italic>Mmp13.</italic> Expression of <italic>Mmp13</italic> in the context of other Mmps during mandibular/alveolar bone development was followed <italic>in vivo</italic> along with <italic>Myb, Sp7</italic> and <italic>Runx2</italic>. The most significant changes were observed in the expression of <italic>Mmp9 and Mmp13</italic>. These MMPs and MYB were further localized <italic>in situ</italic> by immunohistochemistry and were identified in pre/osteoblastic cells as well as in pre/osteocytes. In conclusion, these results provide a comprehensive insight into the expression dynamics of bone related Mmps during mandibular/alveolar bone formation and point to Myb as another potential regulator of Mmp13.</p>