Toll-like receptor 9 deficiency induces osteoclastic bone loss via gut microbiota-associated systemic chronic inflammation.

ABSTRACT: Toll-like receptors (TLRs) play pivotal roles in inflammation and provide important links between the immune and skeletal systems. Although the activation of TLRs may affect osteoclast differentiation and bone metabolism, whether and how TLRs are required for normal bone remodeling remains to be fully explored. In the current study, we show for the first time that TLR9^-/- mice exhibit a low bone mass and low-grade systemic chronic inflammation, which is characterized by the expansion of CD4⁺ T cells and increased levels of inflammatory cytokines, including TNFα, RANKL, and IL1β. The increased levels of these cytokines significantly promote osteoclastogenesis and induce bone loss. Importantly, TLR9 deletion alters the gut microbiota, and this dysbiosis is the basis of

SUBMITTER: Ding P 

PROVIDER: S-EPMC9142495 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature