TY - JOUR
T1 - Optineurin regulates osteoblastogenesis through STAT1
AU - Mizuno, Noriyoshi
AU - Iwata, Tomoyuki
AU - Ohsawa, Ryosuke
AU - Ouhara, Kazuhisa
AU - Matsuda, Shinji
AU - Kajiya, Mikihito
AU - Matsuda, Yukiko
AU - Kume, Kodai
AU - Tada, Yui
AU - Morino, Hiroyuki
AU - Yoshimoto, Tetsuya
AU - Ueki, Yasuyoshi
AU - Mihara, Keichiro
AU - Sotomaru, Yusuke
AU - Takeda, Katsuhiro
AU - Munenaga, Syuichi
AU - Fujita, Tsuyoshi
AU - Kawaguchi, Hiroyuki
AU - Shiba, Hideki
AU - Kawakami, Hideshi
AU - Kurihara, Hidemi
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/5/14
Y1 - 2020/5/14
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2020.03.028
DO - 10.1016/j.bbrc.2020.03.028
M3 - Article
C2 - 32171527
AN - SCOPUS:85081606712
SN - 0006-291X
VL - 525
SP - 889
EP - 894
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -