Osteocytes Produces RANKL Via Wnt-TGFβ Signaling Axis for Osteoclastogenesis.

ABSTRACT: Osteocytes are derived from osteoblasts in the mineralized matrix and are the main source of RANKL required for osteoclastogenesis. We initially found osteocytes as central target cells for Wnt/β-catenin signaling that increases RANKL expression and bone resorption in mice. However, how RANKL is regulated remains unclear. Here, we demonstrated its role and molecular mechanisms using primary osteocytes isolated from long bones. Osteocyte transcriptome sequencing revealed the most associated osteoclast differentiation in KEGG pathways with upregulated expression of Tgfb1/2. In vivo data highlight the specificity of osteocytic Wnt, rather than osteoblastic Wnt, in regulating TGFβ signaling. Activation/inactivation of osteocytic TGFβ signaling stringently promotes/inhibits RANKL

SUBMITTER: Liu Y 

PROVIDER: S-EPMC12509901 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature