Role of Osteocyte-PDL Crosstalk in Tooth Movement via SOST/Sclerostin

N. Odagaki, Yoshihito Ishihara, Z. Wang, E. Ei Hsu Hlaing, M. Nakamura, M. Hoshijima, S. Hayano, N. Kawanabe, H. Kamioka

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)


Sclerostin (Scl) negatively regulates bone formation and favors bone resorption. Osteocytes, the cells responsible for mechanosensing, are known as the primary source of Scl and are a key regulator of bone remodeling through the induction of receptor activator of NF-κB ligand (RANKL). However, the spatiotemporal patterns of Scl in response to mechanical stimuli and their regulatory mechanisms remain unknown. We investigated the regulatory dynamics of the SOST/Scl expression generated by orthodontic tooth movement (OTM) in vivo and in vitro. In 8-wk-old male mice, coil springs were used to move the first molar mesially for 0, 1, 5, or 10 d. A regional histogram and the distribution patterns of the Scl expression showed that the Scl expression in the alveolar bone was increased on the compression side and peaked on day 5, with a gradual increase in the degree of significance. On day 10, the expression around the periodontal ligament (PDL)–alveolar bone boundary returned to the control level. Conversely, the expression of Scl on the tension side was only significantly decreased on day 1. Compressive force biphasically modulated the SOST/Scl expression in the isolated human PDL and thereby upregulated osteocytic SOST via paracrine activation in an osteocyte-PDL co-culture system designed to mimic OTM. This system did not affect the RANKL or OPG expression in osteocytes, suggesting that the bone resorption pathways are acted upon in a PDL-dependent and osteocyte-independent manner through RANKL/OPG signaling. Moreover, sclerostin neutralizing antibody significantly attenuated the upregulation of SOST that was induced by compressive force. In conclusion, our results provide evidence to support that factors secreted by the PDL, including SOST/Scl, control alveolar bone remodeling through osteocytic SOST/Scl in OTM.

Original languageEnglish
Pages (from-to)1374-1382
Number of pages9
JournalJournal of dental research
Issue number12
Publication statusPublished - Nov 1 2018


  • RANK ligand
  • Wnt signaling pathway
  • cellular mechanotransduction
  • osteocytes
  • paracrine communication
  • periodontal ligament cells

ASJC Scopus subject areas

  • General Dentistry


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