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

Nat Commun. 2025 Jan 2;16(1):9. doi: 10.1038/s41467-024-55451-z.

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.

MeSH terms

  • Animals
  • Bone Diseases, Metabolic / genetics
  • Bone Diseases, Metabolic / metabolism
  • Bone Diseases, Metabolic / pathology
  • Bone Remodeling / genetics
  • Cell Differentiation*
  • Core Binding Factor Alpha 1 Subunit* / genetics
  • Core Binding Factor Alpha 1 Subunit* / metabolism
  • Humans
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein / genetics
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteoblasts* / metabolism
  • Osteoclasts* / cytology
  • Osteoclasts* / metabolism
  • Osteogenesis* / genetics
  • Sp7 Transcription Factor* / genetics
  • Sp7 Transcription Factor* / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Sp7 Transcription Factor
  • Core Binding Factor Alpha 1 Subunit
  • Sp7 protein, mouse
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • Runx2 protein, mouse
  • Transcription Factors