Deletion of absent in melanoma-2 (AIM2) drives bone marrow adipogenesis and impairs bone microarchitecture

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Absent in melanoma (AIM) 2, a gene induced by interferon, acts as a cytosolic sensor for double-stranded (ds) DNA. It forms the AIM2 inflammasome, producing interleukin (IL)-1β and IL-18. Our previous study demonstrated that mice lacking AIM2 exhibit spontaneous obesity, insulin resistance, and inflammation in adipose tissue. In this study, we aimed to explore the impact of AIM2 gene deletion on the bone marrow microenvironment and bone morphology in adult and aged mice. Utilizing micro-computed tomography (micro-CT), we discovered that female mice lacking AIM2 showed an increase in the total cross-sectional area at 5 months of age, accompanied by an increase in cortical thickness in the mid-diaphysis of the femur at both 5 and 15 months of age. At 15 months, the cortical bone mineral density (BMD) significantly decreased in AIM2 null females compared to wildtype (WT) mice. Trabecular bone volume and BMD at the distal metaphysis of the femur and the lumbar vertebra-4 were also significantly decreased in AIM2 null females. Histological examination of femurs from aged mice demonstrated increased bone marrow adiposity in AIM2 null mice, accompanied by a significant increase in CD45 - /CD31 - /Sca1 + /Pdgfa + adipogenic progenitor cells and a decrease in the ratio of CD45 - /CD31 - /Sca1 - /Pdgfa + osteogenic progenitor cells, as determined by flow cytometry of bone marrow cells. R

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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