Elevation of master autophagy regulator Tfeb in osteoblast lineage cells increases bone mass and strength.

ABSTRACT: Autophagy is a recycling pathway in which damaged proteins, protein aggregates, and organelles are delivered to lysosomes for degradation. Autophagy insufficiency is thought to contribute to osteoporosis. Accordingly, autophagy elimination from the osteoblast lineage reduces bone formation and bone mass. However, whether increasing autophagy would benefit bone health is unknown. Here, we increased expression of endogenous transcription factor EB gene (Tfeb) in osteoblast lineage cells in vivo via CRISPR activation (TfebCRa mice). Elevated Tfeb stimulated autophagy and lysosomal biogenesis in osteoblasts. TfebCRa mice displayed a robust increase in femoral and vertebral cortical thickness at 4.5 months of age. Increases in cortical thickness were due to increased periosteal bone formation.

SUBMITTER: James A 

PROVIDER: S-EPMC12487674 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature