Nuclear β-catenin translocation plays a key role in osteoblast differentiation of giant cell tumor of bone

Atsushi Kimura, Yu Toda, Yoshihiro Matsumoto, Hidetaka Yamamoto, Kenichiro Yahiro, Eijiro Shimada, Masaya Kanahori, Ryunosuke Oyama, Suguru Fukushima, Makoto Nakagawa, Nokitaka Setsu, Makoto Endo, Toshifumi Fujiwara, Tomoya Matsunobu, Yoshinao Oda, Yasuharu Nakashima

Research output: Contribution to journalArticlepeer-review

Abstract

Denosumab is a game-changing drug for giant cell tumor of bone (GCTB); however, its clinical biomarker regarding tumor ossification of GCTB has not been elucidated. In this study, we investigated the relationship between Wnt/β-catenin signaling and the ossification of GCTB and evaluated whether endogenous nuclear β-catenin expression predicted denosumab-induced bone formation in GCTB. Genuine patient-derived primary GCTB tumor stromal cells exhibited osteoblastic characteristics. Identified osteoblastic markers and nuclear β-catenin translocation were significantly upregulated via differentiation induction and were inhibited by treating with Wnt signaling inhibitor, GGTI-286, or selective Rac1-LEF inhibitor, NSC23766. Furthermore, we reviewed the endogenous ossification and nuclear β-catenin translocation of 86 GCTB clinical samples and elucidated that intra-tumoral ossification was significantly associated with the nuclear translocation. Three-dimensional quantitative analyses (n = 13) of tumoral CT images have revealed that the nuclear β-catenin translocation of naïve GCTB samples was significantly involved with the denosumab-induced tumor ossification. Our findings suggest a close relationship between the nuclear β-catenin translocation and the osteoblastic differentiation of GCTB. Investigations of the nuclear β-catenin in naïve GCTB samples may provide a promising biomarker for predicting the ossification of GCTB following denosumab treatment.

Original languageEnglish
Article number13438
JournalScientific reports
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2022

All Science Journal Classification (ASJC) codes

  • General

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