Expression of the aryl hydrocarbon receptor in Osterix-lineage cells regulates adult skeletal homeostasis in a compartment-specific manner.

ABSTRACT: Kynurenine (KYN), a tryptophan metabolite that increases with age, impairs osteoblast function. The aryl hydrocarbon receptor (AhR) has been proposed to mediate KYN's actions in bone. To test whether deletion of AhR in osteoblasts is beneficial for bone, we established an adult-onset AhR conditional knockout (CKO) model using Osx-Cre and examined the effects of AhR CKO at 4.5 and 6 mo of age (representing ~6 and 12 wk of CKO). While BMSC-derived osteoblasts from WT mice demonstrated reduced matrix formation from KYN treatment, AhR CKO osteoblasts were unaffected by KYN. Kynurenine's harmful effects were most pronounced in the middle of an osteoblastic differentiation time course, and these effects could be rescued via the AhR antagonist BAY2416964. In vivo, AhR deletion in Osx-expressing c

SUBMITTER: Dorn J 

PROVIDER: S-EPMC12105101 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature