beta2-adrenergic receptor knockout aggravates osteoarthritis-characteristic bone changes in mice

Objectives We have shown previously that the elimination of peripheral sympathetic nerve fibers by chemical sympathectomy (Syx) aggravates osteoarthritis (OA) characteristic subchondral bone changes after OA induction in mice: Bone volume to tissue volume (BV/TV) increased by 13% and on the other hand trabecular space (TbSp) decreased by 22%. Additionaly, Syx lead to norepinephrine (NE) reduction by 54%. However, the adrenergic receptor which mediates these effects is still not clear. In previous studies it has been demonstrated that the beta2-adrenergic receptor plays a major role in bone remodeling. The aim of this study was to analyze the contribution of the beta2-adrenergic receptor to the Syx phenotype after experimental OA induction in a mouse model.

Methods OA was induced in homozygous beta2-adrenergic receptor knockout mice (Adrb2-/-) by the destabilization of the medial meniscus (DMM). OA-characteristic subchondral bone changes were assessed by micro-CT 8 weeks post-DMM. Additionally, NE concentration in spleen samples was measured in DMM-operated and untreated Adrb2-/- mice after 8 weeks.

Results and Conclusion Micro-CT analyses revealed a significant increase of BV/TV compared to WT (20%) and Syx mice (6%) after DMM surgery. Further, TbSp was significantly decreased in Adrb2-/- mice compared to WT (60%) and Syx mice (51%) after DMM surgery. Spleen NE in Adrb2-/- mice was reduced to 60% of WT 8 weeks after DMM, similar to Syx (54%) (NE/spleen weight/body weight). In contrast, absence of beta2-adrenergic receptor had no influence on splenic NE concentration in untreated mice. Taken together, beta2-adrenergic receptor deficiency aggravated OA-characteristic bone changes after DMM surgery compared to WT mice. Interestingly, these changes were even more pronounced than in Syx mice suggesting that the beta2-adrenergic receptor plays a major role and is thus an attractive target for the development of novel therapeutic options. The contribution of other receptor subtypes has to be investigated in the future.

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Artikel online veröffentlicht:
15. Oktober 2020