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

Yu Yamashita, Mikihito Hayashi (), Anhao Liu, Fumiyuki Sasaki, Yosuke Tsuchiya, Hiroshi Takayanagi, Mitsuru Saito and Tomoki Nakashima ()
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Yu Yamashita: Institute of Science Tokyo
Mikihito Hayashi: Institute of Science Tokyo
Anhao Liu: Institute of Science Tokyo
Fumiyuki Sasaki: Institute of Science Tokyo
Yosuke Tsuchiya: Institute of Science Tokyo
Hiroshi Takayanagi: The University of Tokyo
Mitsuru Saito: The Jikei University School of Medicine
Tomoki Nakashima: Institute of Science Tokyo

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-024-55451-z

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