Z Orthop Unfall 2020; 158(S 01): S212
DOI: 10.1055/s-0040-1719204
Vortrag
DKOU20-1000 Grundlagenforschung->27. Arthrose

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

K Bagdadi El
*   präsentierender Autor
1   Orthopedic University Hospital Friedrichsheim, Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Frankfurt am Main
,
D Muschter
2   University Regensburg, Department of Orthopedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology, Regensburg
,
C Dorn
3   University of Regensburg, Institute of Pharmacy, Regensburg
,
S Grässel
2   University Regensburg, Department of Orthopedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology, Regensburg
,
A Meurer
1   Orthopedic University Hospital Friedrichsheim, Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Frankfurt am Main
,
RH Straub
4   Department of Internal Medicine I, Lab of Experimental Rheumatology &Neuroendocrine Immunology, University Hospital Regensburg, Regensburg
,
F Zaucke
1   Orthopedic University Hospital Friedrichsheim, Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Frankfurt am Main
,
Z Jenei-Lanzl
1   Orthopedic University Hospital Friedrichsheim, Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Frankfurt am Main
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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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Publication History

Article published online:
15 October 2020

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