BMP1 and TLL1 Are Required for Maintaining Periodontal Homeostasis

J. Wang, D. Massoudi, Y. Ren, A. M. Muir, S. E. Harris, D. S. Greenspan, J. Q. Feng

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Mutations in bone morphogenetic protein 1 (BMP1) in humans or deletion of BMP1 and related protease tolloid like 1 (TLL1) in mice lead to osteogenesis imperfecta (OI). Here, we show progressive periodontal defects in mice in which both BMP1 and TLL1 have been conditionally ablated, including malformed periodontal ligament (PDL) (recently shown to play key roles in normal alveolar bone formation), significant loss in alveolar bone mass (P < 0.01), and a sharp reduction in cellular cementum. Molecular mechanism studies revealed a dramatic increase in the uncleaved precursor of type I collagen (procollagen I) and a reduction in dentin matrix protein 1 (DMP1), which is partially responsible for defects in extracellular matrix (ECM) formation and mineralization. We also showed a marked increase in the expression of matrix metallopeptidase 13 (MMP13) and tartrate-resistant acid phosphatase (TRAP), leading to an acceleration in periodontal breakdown. Finally, we demonstrated that systemic application of antibiotics significantly improved the alveolar bone and PDL damage of the knockdown phenotype, which are thus shown to be partially secondary to pathogen-induced inflammation. Together, identification of the novel roles of BMP1 and TLL1 in maintaining homeostasis of periodontal formation, partly via biosynthetic processing of procollagen I and DMP1, provides novel insights into key contributions of the extracellular matrix environment to periodontal homeostasis and contributes toward understanding of the pathology of periodontitis.

Original languageEnglish (US)
Pages (from-to)578-585
Number of pages8
JournalJournal of Dental Research
Volume96
Issue number5
DOIs
StatePublished - May 1 2017
Externally publishedYes

Keywords

  • ECM
  • craniofacial biology/genetics
  • inflammation
  • matrix biology
  • mineralized tissue/development
  • periodontal tissues/periodontium

ASJC Scopus subject areas

  • Dentistry(all)

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    Wang, J., Massoudi, D., Ren, Y., Muir, A. M., Harris, S. E., Greenspan, D. S., & Feng, J. Q. (2017). BMP1 and TLL1 Are Required for Maintaining Periodontal Homeostasis. Journal of Dental Research, 96(5), 578-585. https://doi.org/10.1177/0022034516686558