Removal of SOST or blocking its product sclerostin rescues defects in the periodontitis mouse model

Yinshi Ren, Xianglong Han, Sunita P. Ho, Stephen E. Harris, Zhengguo Cao, Aris N. Economides, Chunlin Qin, Huazhu Ke, Min Liu, Jian Q. Feng

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Understanding periodontal ligament (PDL) biology and developing an effective treatment for bone and PDL damage due to periodontitis have been longstanding aims in dental medicine. Here, we first demonstrated by cell lineage tracing and mineral doublelabeling approaches that murine PDL progenitor cells display a 2- and 3-fold higher mineral deposition rate than the periosteum and endosteum at the age of 4 weeks, respectively. We next proved that the pathologic changes in osteocytes (Ocys; changes from a spindle shape to round shape with a >50% reduction in the dendrite number/length, and an increase in SOST) are the key pathologic factors responsible for bone and PDL damage in periostin-null mice (a periodontitis animal model) using a newly developed 3-dimensional FITCImaris technique. Importantly, we proved that deleting the Sost gene (a potent inhibitor of WNT signaling) or blocking sclerostin function by using the mAb in this periodontitis model significantly restores bone and PDL defects (n = 4-5; P < 0.05). Together, identification of the key contribution of the PDL in normal alveolar bone formation, the pathologic changes of the Ocys in periodontitis bone loss, and the novel link between sclerostin and Wnt signaling in the PDL will aid future drug development in the treatment of patients with periodontitis.

Original languageEnglish (US)
Pages (from-to)2702-2711
Number of pages10
JournalFASEB Journal
Volume29
Issue number7
DOIs
StatePublished - Jul 1 2015
Externally publishedYes

Keywords

  • Alveolar bone
  • PDL
  • Periostin

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Removal of SOST or blocking its product sclerostin rescues defects in the periodontitis mouse model'. Together they form a unique fingerprint.

  • Cite this

    Ren, Y., Han, X., Ho, S. P., Harris, S. E., Cao, Z., Economides, A. N., Qin, C., Ke, H., Liu, M., & Feng, J. Q. (2015). Removal of SOST or blocking its product sclerostin rescues defects in the periodontitis mouse model. FASEB Journal, 29(7), 2702-2711. https://doi.org/10.1096/fj.14-265496