Impaired bone healing upon neutrophil-specific adrenoreceptor beta 2 knockout in non-osteoporotic and osteoporotic mice.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 42209513.
- Also identified by DOI 10.1038/s41536-026-00481-y and PMC identifier 13219604.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
After a bone fracture, osteoporotic mice show delayed healing associated with elevated systemic inflammation and increased neutrophil numbers in the early fracture hematoma. Because short-term treatment with the beta-adrenoreceptor-blocker propranolol reduced neutrophil recruitment, we hypothesized that deletion of β<sub>2</sub>-adrenoreceptor (Adrb2) signaling in neutrophils would normalize neutrophil recruitment and accelerate bone healing in osteoporotic mice. A conditional Adrb2 knockout in Ly6G⁺ neutrophils was generated using Ly6G-Cre Adrb2-flox mice. Bone and immune phenotypes were analyzed via µCT and histology under non-fracture conditions and during bone healing in ovariectomized postmenopausal mice. Both non-osteoporotic and osteoporotic female Ly6G-Adrb2-KO mice showed impaired bone healing vs. controls, while only minor bone alterations were observed under non-fracture conditions. Pathway analysis of isolated neutrophils, characterized by RNA-sequencing, suggested reduced neutrophil activation and disturbed neutrophil/mast cell interactions upon Ly6G-Adrb2-KO. Summarily, our data demonstrate that Adrb2 signaling is important for neutrophil recruitment and seems to be critical for proper bone healing.