Fam102a translocates Runx2 and Rbpjl to facilitate Osterix expression and bone formation

Abstract Bone remodeling maintains the robustness of the bone tissue by balancing bone resorption by osteoclasts and bone formation by osteoblasts. Although these cells together play a crucial role in bone remodeling, only a few reports are available on the common factors involved in the differentia...

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Main Authors: Yu Yamashita, Mikihito Hayashi, Anhao Liu, Fumiyuki Sasaki, Yosuke Tsuchiya, Hiroshi Takayanagi, Mitsuru Saito, Tomoki Nakashima
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-55451-z
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author Yu Yamashita
Mikihito Hayashi
Anhao Liu
Fumiyuki Sasaki
Yosuke Tsuchiya
Hiroshi Takayanagi
Mitsuru Saito
Tomoki Nakashima
author_facet Yu Yamashita
Mikihito Hayashi
Anhao Liu
Fumiyuki Sasaki
Yosuke Tsuchiya
Hiroshi Takayanagi
Mitsuru Saito
Tomoki Nakashima
author_sort Yu Yamashita
collection DOAJ
description Abstract Bone remodeling maintains the robustness of the bone tissue by balancing bone resorption by osteoclasts and bone formation by osteoblasts. Although these cells together play a crucial role in bone remodeling, only a few reports are available on the common factors involved in the differentiation of the two types of cells. Here, we show family with sequence similarity 102 member A (Fam102a) as a bone-remodeling factor that positively regulates both osteoclast and osteoblast differentiation. Fam102a regulates osteoblast differentiation by controlling recombination signal binding protein for immunoglobulin κ J region-like (Rbpjl). The Fam102a-Rbpjl axis promotes the nuclear translocation of transcription factors and enhances the expression of Osterix, a transcription factor essential for osteoblast differentiation. The deletion of Fam102a or a functional mutation in Rbpjl leads to osteopenia accompanied by reduced osteoblastic bone formation. Thus, the Fam102a-Rbpjl axis plays an important role in osteoblasts and this finding provides insights into bone remodeling.
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institution Kabale University
issn 2041-1723
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publishDate 2025-01-01
publisher Nature Portfolio
record_format Article
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spelling doaj-art-1016991aa4a44039a0d4ea463f75a8842025-01-05T12:39:44ZengNature PortfolioNature Communications2041-17232025-01-0116111410.1038/s41467-024-55451-zFam102a translocates Runx2 and Rbpjl to facilitate Osterix expression and bone formationYu Yamashita0Mikihito Hayashi1Anhao Liu2Fumiyuki Sasaki3Yosuke Tsuchiya4Hiroshi Takayanagi5Mitsuru Saito6Tomoki Nakashima7Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Institute of Science TokyoDepartment of Cell Signaling, Graduate School of Medical and Dental Sciences, Institute of Science TokyoDepartment of Cell Signaling, Graduate School of Medical and Dental Sciences, Institute of Science TokyoDepartment of Cell Signaling, Graduate School of Medical and Dental Sciences, Institute of Science TokyoDepartment of Cell Signaling, Graduate School of Medical and Dental Sciences, Institute of Science TokyoDepartment of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of TokyoDepartment of Orthopaedic Surgery, The Jikei University School of MedicineFaculty of Dentistry, Institute of Science TokyoAbstract Bone remodeling maintains the robustness of the bone tissue by balancing bone resorption by osteoclasts and bone formation by osteoblasts. Although these cells together play a crucial role in bone remodeling, only a few reports are available on the common factors involved in the differentiation of the two types of cells. Here, we show family with sequence similarity 102 member A (Fam102a) as a bone-remodeling factor that positively regulates both osteoclast and osteoblast differentiation. Fam102a regulates osteoblast differentiation by controlling recombination signal binding protein for immunoglobulin κ J region-like (Rbpjl). The Fam102a-Rbpjl axis promotes the nuclear translocation of transcription factors and enhances the expression of Osterix, a transcription factor essential for osteoblast differentiation. The deletion of Fam102a or a functional mutation in Rbpjl leads to osteopenia accompanied by reduced osteoblastic bone formation. Thus, the Fam102a-Rbpjl axis plays an important role in osteoblasts and this finding provides insights into bone remodeling.https://doi.org/10.1038/s41467-024-55451-z
spellingShingle Yu Yamashita
Mikihito Hayashi
Anhao Liu
Fumiyuki Sasaki
Yosuke Tsuchiya
Hiroshi Takayanagi
Mitsuru Saito
Tomoki Nakashima
Fam102a translocates Runx2 and Rbpjl to facilitate Osterix expression and bone formation
Nature Communications
title Fam102a translocates Runx2 and Rbpjl to facilitate Osterix expression and bone formation
title_full Fam102a translocates Runx2 and Rbpjl to facilitate Osterix expression and bone formation
title_fullStr Fam102a translocates Runx2 and Rbpjl to facilitate Osterix expression and bone formation
title_full_unstemmed Fam102a translocates Runx2 and Rbpjl to facilitate Osterix expression and bone formation
title_short Fam102a translocates Runx2 and Rbpjl to facilitate Osterix expression and bone formation
title_sort fam102a translocates runx2 and rbpjl to facilitate osterix expression and bone formation
url https://doi.org/10.1038/s41467-024-55451-z
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