Optineurin regulates osteoblastogenesis through STAT1
| Autor: | Katsuhiro Takeda, Hideshi Kawakami, Yasuyoshi Ueki, Yusuke Sotomaru, Shinji Matsuda, Tetsuya Yoshimoto, Keichiro Mihara, Yui Tada, Noriyoshi Mizuno, Ryosuke Ohsawa, Hiroyuki Kawaguchi, Hideki Shiba, Hiroyuki Morino, Tomoyuki Iwata, Mikihito Kajiya, Syuichi Munenaga, Kodai Kume, Hidemi Kurihara, Tsuyoshi Fujita, Kazuhisa Ouhara, Yukiko Matsuda |
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| Rok vydání: | 2020 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Biophysics Osteoclasts Cell Cycle Proteins Core Binding Factor Alpha 1 Subunit Biochemistry Bone resorption Bone remodeling 03 medical and health sciences 0302 clinical medicine Osteoclast Osteogenesis medicine Animals Molecular Biology Transcription factor Cells Cultured Optineurin Osteoblasts Chemistry Membrane Transport Proteins Osteoblast Cell Differentiation Cell Biology Mice Mutant Strains Cell biology RUNX2 Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure STAT1 Transcription Factor 030220 oncology & carcinogenesis STAT protein |
| Zdroj: | Biochemical and biophysical research communications. 525(4) |
| ISSN: | 1090-2104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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