Inhibition of STAT1 accelerates bone fracture healing

Kosuke Tajima, Hironari Takaishi, Jiro Takito, Takahide Tohmonda, Masaki Yoda, Norikazu Ota, Naoto Kosaki, Morio Matsumoto, Hiroyasu Ikegami, Toshiyasu Nakamura, Tokuhiro Kimura, Yasunori Okada, Keisuke Horiuchi, Kazuhiro Chiba, Yoshiaki Toyama

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Skeletal fracture healing involves a variety of cellular and molecular events; however, the mechanisms behind these processes are not fully understood. In the current study, we investigated the potential involvement of the signal transducer and activator of transcription 1 (STAT1), a critical regulator for both osteoclastogenesis and osteoblast differentiation, in skeletal fracture healing. Weused a fracture model and a cortical defect model in mice, and found that fracture callus remodeling and membranous ossification are highly accelerated in STAT1-deficient mice. Additionally, we found that STAT1 suppresses Osterix transcript levels and Osterix promoter activity in vitro, indicating the suppression of Osterix transcription as one of the mechanisms behind the inhibitory effect of STAT1 on osteoblast differentiation. Furthermore, we found that fludarabine, a potent STAT1 inhibitor, significantly increases bone formation in a heterotopic ossification model. These results reveal previously unknown functions of STAT1 in skeletal homeostasis and may have important clinical implications for the treatment of skeletal bone fracture.

Original languageEnglish
Pages (from-to)937-941
Number of pages5
JournalJournal of Orthopaedic Research
Volume28
Issue number7
DOIs
Publication statusPublished - 2010 Jul

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STAT1 Transcription Factor
Fracture Healing
Bone Fractures
Osteogenesis
Osteoblasts
Heterotopic Ossification
Bony Callus
Homeostasis

Keywords

  • Fludarabine
  • NF-κB p65
  • Osterix
  • Skeletal fracture healing
  • STAT1

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Tajima, K., Takaishi, H., Takito, J., Tohmonda, T., Yoda, M., Ota, N., ... Toyama, Y. (2010). Inhibition of STAT1 accelerates bone fracture healing. Journal of Orthopaedic Research, 28(7), 937-941. https://doi.org/10.1002/jor.21086

Inhibition of STAT1 accelerates bone fracture healing. / Tajima, Kosuke; Takaishi, Hironari; Takito, Jiro; Tohmonda, Takahide; Yoda, Masaki; Ota, Norikazu; Kosaki, Naoto; Matsumoto, Morio; Ikegami, Hiroyasu; Nakamura, Toshiyasu; Kimura, Tokuhiro; Okada, Yasunori; Horiuchi, Keisuke; Chiba, Kazuhiro; Toyama, Yoshiaki.

In: Journal of Orthopaedic Research, Vol. 28, No. 7, 07.2010, p. 937-941.

Research output: Contribution to journalArticle

Tajima, K, Takaishi, H, Takito, J, Tohmonda, T, Yoda, M, Ota, N, Kosaki, N, Matsumoto, M, Ikegami, H, Nakamura, T, Kimura, T, Okada, Y, Horiuchi, K, Chiba, K & Toyama, Y 2010, 'Inhibition of STAT1 accelerates bone fracture healing', Journal of Orthopaedic Research, vol. 28, no. 7, pp. 937-941. https://doi.org/10.1002/jor.21086
Tajima K, Takaishi H, Takito J, Tohmonda T, Yoda M, Ota N et al. Inhibition of STAT1 accelerates bone fracture healing. Journal of Orthopaedic Research. 2010 Jul;28(7):937-941. https://doi.org/10.1002/jor.21086
Tajima, Kosuke ; Takaishi, Hironari ; Takito, Jiro ; Tohmonda, Takahide ; Yoda, Masaki ; Ota, Norikazu ; Kosaki, Naoto ; Matsumoto, Morio ; Ikegami, Hiroyasu ; Nakamura, Toshiyasu ; Kimura, Tokuhiro ; Okada, Yasunori ; Horiuchi, Keisuke ; Chiba, Kazuhiro ; Toyama, Yoshiaki. / Inhibition of STAT1 accelerates bone fracture healing. In: Journal of Orthopaedic Research. 2010 ; Vol. 28, No. 7. pp. 937-941.
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