Optineurin regulates osteoblastogenesis through STAT1

Noriyoshi Mizuno, Tomoyuki Iwata, Ryosuke Ohsawa, Kazuhisa Ouhara, Shinji Matsuda, Mikihito Kajiya, Yukiko Matsuda, Kodai Kume, Yui Tada, Hiroyuki Morino, Tetsuya Yoshimoto, Yasuyoshi Ueki, Keichiro Mihara, Yusuke Sotomaru, Katsuhiro Takeda, Syuichi Munenaga, Tsuyoshi Fujita, Hiroyuki Kawaguchi, Hideki Shiba, Hideshi KawakamiHidemi Kurihara

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

A sophisticated and delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts regulates bone metabolism. Optineurin (OPTN) is a gene involved in primary open-angle glaucoma and amyotrophic lateral sclerosis. Although its function has been widely studied in ophthalmology and neurology, recent reports have shown its possible involvement in bone metabolism through negative regulation of osteoclast differentiation. However, little is known about the role of OPTN in osteoblast function. Here, we demonstrated that OPTN controls not only osteoclast but also osteoblast differentiation. Different parameters involved in osteoblastogenesis and osteoclastogenesis were assessed in Optn−/- mice. The results showed that osteoblasts from Optn−/- mice had impaired alkaline phosphatase activity, defective mineralized nodules, and inability to support osteoclast differentiation. Moreover, OPTN could bind to signal transducer and activator of transcription 1 (STAT1) and regulate runt-related transcription factor 2 (RUNX2) nuclear localization by modulating STAT1 levels in osteoblasts. These data suggest that OPTN is involved in bone metabolism not only by regulating osteoclast function but also by regulating osteoblast function by mediating RUNX2 nuclear translocation via STAT1.

Original languageEnglish
Pages (from-to)889-894
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume525
Issue number4
DOIs
Publication statusPublished - 14-05-2020

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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