Acyloxyacyl hydrolase deficiency induces chronic inflammation and bone loss in male mice.

Xu Cheng, Xiaoting Song, Zhiyan Li, Chiting Yuan, Xinhuan Lei, Mingxuan Feng, Zhenghua Hong, Liwei Zhang, Dun Hong

Journal of molecular medicine (Berlin, Germany) 2022 Nov

filter terms:

Hormonal homeostasis is essential in bone remodeling. Recent studies have shown that the treatment of intestinal inflammation can result in the regulation of bone resorption in distant bones. Increased intestinal permeability may lead to systemic inflammation and bone loss, also known as gut-bone axis. However, the underlying mechanism remains to be elucidated. Lipopolysaccharide (LPS) is a component of gram-negative bacteria that can increase osteoclastic differentiation in vitro. Acyloxyacyl hydrolase (AOAH) is a specific degrading enzyme of LPS, but little is known about the role of AOAH in bone metabolism. In this study, adult Aoah-/- mice showed a chronic inflammatory state and osteopenic phenotype analyzed by micro-CT and HE staining. Tartrate-resistant acid phosphatase (TRAP) staining of femurs showed an increase in TRAP-positive cells from Aoah-/- mice. AOAH depletion enhanced the osteoclast differentiation and bone resorption capacity of bone marrow-derived macrophages (BMMs). The enhanced osteoclast differentiation and bone resorption capacity of Aoah-/- BMMs were reversed by rAOAH. In conclusion, the chronic inflammatory state of adult Aoah-/- mice promotes bone resorption. AOAH participates in bone metabolism, which is mainly mediated by inhibiting osteoclast differentiation. LPS may be a key mediator of the gut-bone axis, and targeting AOAH may represent a feasible strategy for the treatment of chronic inflammatory bone resorption. KEY MESSAGES : AOAH knockout mice exhibited chronic inflammation mediated by LPS, and LPS may also serve as an important mediator in the regulation of bone metabolism in the gut-bone axis. AOAH regulated bone resorption by blocking the osteoclast differentiation via classical ERK and JNK pathways. rAOAH could rescue the enhanced osteoclast differentiation caused by AOAH deficiency. © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Citation

Xu Cheng, Xiaoting Song, Zhiyan Li, Chiting Yuan, Xinhuan Lei, Mingxuan Feng, Zhenghua Hong, Liwei Zhang, Dun Hong. Acyloxyacyl hydrolase deficiency induces chronic inflammation and bone loss in male mice. Journal of molecular medicine (Berlin, Germany). 2022 Nov;100(11):1599-1616