Inhibition of C5AR1 impairs osteoclast mobilization and prevents bone loss.

ABSTRACT: Age-related and chemotherapy-induced bone loss depends on cellular senescence and the cell secretory phenotype. However, the factors secreted in the senescent microenvironment that contribute to bone loss remain elusive. Here, we report a central role for the inflammatory alternative complement system in skeletal bone loss. Through transcriptomic analysis of bone samples, we identified complement factor D, a rate-limiting factor of the alternative pathway of complement, which is among the most responsive factors to chemotherapy or estrogen deficiency. We show that osteoblasts and osteocytes are major inducers of complement activation, while monocytes and osteoclasts are their primary targets. Genetic deletion of C5ar1, the receptor of the anaphylatoxin C5a, or treatment with a C5AR1 inhibi

SUBMITTER: Pimenta-Lopes C 

PROVIDER: S-EPMC10422003 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature