gms | German Medical Science

German Congress of Orthopaedics and Traumatology (DKOU 2019)

22. - 25.10.2019, Berlin

Analysis of P2X7 Receptor and Panx1 Expression in Osteoporosis

Meeting Abstract

  • presenting/speaker Muyao Tang - Experimental Trauma Surgery, Justus-Liebig-University, Giessen, Germany
  • Vivien Kauschke - Experimental Trauma Surgery, Justus-Liebig-University, Giessen, Germany
  • Thaqif El Khassawna - Experimental Trauma Surgery, Justus-Liebig-University, Giessen, Germany
  • Christian Heiß - University Hospital of Giessen-Marburg GmbH, Campus Giessen, Department of Trauma, Hand and Reconstructive Surgery, Experimental Trauma Surgery, Gießen, Germany
  • Katrin Lips - Experimental Trauma Surgery, Justus-Liebig-University, Giessen, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2019). Berlin, 22.-25.10.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocAB48-53

doi: 10.3205/19dkou445, urn:nbn:de:0183-19dkou4451

Published: October 22, 2019

© 2019 Tang et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objectives: Osteoporosis, characterized by bone mineral density decrease, leads to a high risk of bone fracture. It is now widely recognized that purinergic signaling plays an important role in the regulation of bone remodeling [1]. One receptor subtype, P2X receptor is considered to be important in relation to osteoporosis. Activated Pannexin1 (Panx1) channels provide a pathway which accounts for sustained activation of P2X receptors. Therefore, we hypothesize that the expression of P2X7 receptor and Panx1 is regulated in samples of osteoporosis.

Methods: Mesenchymal stem cells (MSC) were isolated from samples of 10 female patients, among which 5 were osteoporotic. Samples were collected during routine clinical fracture treatment (approved by ethics commission AZ 74/09). As a second model we used 45-48 week old female rats with an induction of osteoporosis by ovariectomy and malnutrition. The 28 rats were put into 4 groups: (i) sham group (n=7), (ii) ovariectomy group (OVX, n=6), (iii) diet group (calcium, vitamin D and phosphate deficient diet, n=7) and (iv) ovariectomy with diet group (OVXD, n=8). The samples were collected after 3 months. Finally, an implant associated fracture model of genetically osteoporotic mice (KO, n=12) and their corresponding wildtypes (WT, n=12) was used that was established recently [2]. RNA was isolated from the bone and cell culture samples and the expression of P2X7 receptor and Panx1 was investigated by real-time RT-PCR. For statistical analysis Kruskal-Wallis test and Mann- Whitney U test were used (SPSS Inc., version 23, Chicago, IL, USA). P-values ≤ 0.05 were considered statistically significant.

Results and conclusion: Of human groups, there were no statistically significant changes in the expression of P2X7 (P=1) and Panx1 (P=0.69) because of high donor variance and low sample number.

In rat osteoporosis model, in P2X7, there was a statistically significant down regulation in the Diet group (P=0.005) and OVXD group (P=0.02) compared to Sham group. There was also a statistically significant down regulation in the OVXD group compared to OVX (P=0.045). In Panx1, there was a statistically significant down regulation in the OVXD group compared to OVX (P=0.002).

In the mouse osteoporosis fracture model, in P2X7, there was a statistically significant up regulation in the KO group compared to the WT (P=0.002). And in Panx1, there was a statistically significant down regulation in the KO group compared to the WT (P=0.026).

These results indicate that P2X7 receptor and Panx1 contribute to osteoporosis in the animal models. The increase of P2X7 and Panx1 in rat might help to establish new therapeutic strategies for osteoporosis. In humans, it is necessary to increase the number of samples because of the high donor variance. This might then lead to relevant and statistically significant results.


References

1.
Burnstock G, Arnett TR, Orriss IR. Purinergic signalling in the musculoskeletal system. Purinergic Signal. 2013 Dec;9(4):541-72. DOI: 10.1007/s11302-013-9381-4 External link
2.
Kauschke V, Schneider M, Jauch A, Schumacher M, Kampschulte M, Rohnke M, Henss A, Bamberg C, Trinkaus K, Gelinsky M, Heiss C, Lips KS. Effects of a Pasty Bone Cement Containing Brain-Derived Neurotrophic Factor-Functionalized Mesoporous Bioactive Glass Particles on Metaphyseal Healing in a New Murine Osteoporotic Fracture Model. Int J Mol Sci. 2018 Nov 9;19(11). pii: E3531. DOI: 10.3390/ijms19113531 External link