Background The pathogenesis of osteoporosis is complex and involves age-related factors and inflammation. 12/15-lipoxygenase (12/15-LOX) plays a key role in the regulation of inflammatory response and has been shown to contribute in bone metabolisms. However, the exact role of 12/15-LOX in the pathogenesis of osteoporosis is not clear.
Objectives We aimed to investigate the impact of genetic deletion of 12/15-LOX on 1) bone mineral density (BMD) and 2) serum balance between osteoprotegerin (OPG) and RANK ligand (RANKL), the two proteins known to be involved in bone remodelling, in mice.
Methods The whole body BMD was measured using dual-energy X-ray absorptiometry (DEXA) bone densitometer equipped with software for evaluation of small animals (Hologic Discovery, USA) in 40-weeks old 12/15-LOX knockout mice and their age- and sex-matched wild-type littermates (C57Bl mice). Serum concentrations of OPG and RANKL were measured using commercially available ELISA kits (R&D Systems and USCN Life Science Inc., respectively).
Results The mean whole body BMD was significantly lower in female 12/15-LOX knockout mice as compared with age-matched female C57Bl mice (p<0.01). No significant differences were found in the mean whole body BMD of male 12/15-LOX knockout mice as compared with their age-matched male wild-type littermates.
No significant difference could be found in the mean serum concentration of OPG between 40-weeks old female 12/15-LOX knockout and C57Bl mice. However, in younger (8-weeks old) female C57Bl mice the mean serum concentration of OPG was significantly higher as compared with female 12/15-LOX knockout mice of the same age as well as compared with female 40-weeks old C57Bl or 12/15-LOX knockout animals (p<0.01 for all comparisons).
There were no significant differences in the mean serum concentration of RANKL between female 12/15-LOX knockout mice and their wildtype littermates.
Conclusions The results of our study indicate that 12/15-LOX plays a role in age-related osteoporosis in female mice, possibly through regulation of OPG-RANKL balance. Further studies should address the role of hormonal status on 12/15-LOX interactions with OPG-RANKL pathway.
Disclosure of Interest None declared
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