Yamashita Yu, Hayashi Mikihito, Liu Anhao, Sasaki Fumiyuki, Tsuchiya Yosuke, Takayanagi Hiroshi, Saito Mitsuru, Nakashima Tomoki
Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan.
Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo, Japan.
Nat Commun. 2025 Jan 2;16(1):9. doi: 10.1038/s41467-024-55451-z.
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.
骨重塑通过平衡破骨细胞的骨吸收和成骨细胞的骨形成来维持骨组织的强健性。尽管这两种细胞在骨重塑过程中共同发挥着关键作用，但关于这两种细胞分化所涉及的共同因素的报道却很少。在此，我们展示了序列相似性家族102成员A（Fam102a）作为一种骨重塑因子，它对破骨细胞和成骨细胞的分化均具有正向调节作用。Fam102a通过控制免疫球蛋白κJ区域样重组信号结合蛋白（Rbpjl）来调节成骨细胞的分化。Fam102a-Rbpjl轴促进转录因子的核转位，并增强Osterix的表达，Osterix是成骨细胞分化所必需的一种转录因子。Fam102a的缺失或Rbpjl中的功能性突变会导致骨质减少，并伴有成骨细胞骨形成减少。因此，Fam102a-Rbpjl轴在成骨细胞中发挥着重要作用，这一发现为骨重塑提供了新的见解。
