Osteocyte Regulation of Receptor Activator of NF-κB Ligand/Osteoprotegerin in a Sheep Model of Osteoporosis.

Autor:	El Khassawna T; Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig University of Giessen, Giessen, Germany. Electronic address: thaqif.elkhassawna@chiru.med.uni-giessen.de., Merboth F; Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig University of Giessen, Giessen, Germany., Malhan D; Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig University of Giessen, Giessen, Germany., Böcker W; Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig University of Giessen, Giessen, Germany; Department of General Surgery, Traumatology and Reconstructive Surgery, Ludwig Maximilian University of Munich, Munich, Germany., Daghma DES; Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig University of Giessen, Giessen, Germany., Stoetzel S; Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig University of Giessen, Giessen, Germany., Kern S; Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig University of Giessen, Giessen, Germany., Hassan F; Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig University of Giessen, Giessen, Germany., Rosenbaum D; Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig University of Giessen, Giessen, Germany., Langenstein J; Department of Veterinary Clinical Sciences, Clinical Pathology and Clinical Pathophysiology, Justus-Liebig University of Giessen, Giessen, Germany., Bauer N; Department of Veterinary Clinical Sciences, Clinical Pathology and Clinical Pathophysiology, Justus-Liebig University of Giessen, Giessen, Germany., Schlagenhauf A; Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig University of Giessen, Giessen, Germany., Rösen-Wolff A; Department of Pediatrics, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany., Schulze F; Department of Pediatrics, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany., Rupp M; Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig University of Giessen, Giessen, Germany; Department of Trauma, Hand and Reconstructive Surgery, University Hospital of Giessen-Marburg, Giessen, Germany., Hose D; Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany., Secklinger A; Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany., Ignatius A; Institute of Orthopedic Research and Biomechanics, Trauma Research Centre, University of Ulm, Ulm, Germany., Wilke HJ; Institute of Orthopedic Research and Biomechanics, Trauma Research Centre, University of Ulm, Ulm, Germany., Lips KS; Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig University of Giessen, Giessen, Germany., Heiss C; Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig University of Giessen, Giessen, Germany; Department of Trauma, Hand and Reconstructive Surgery, University Hospital of Giessen-Marburg, Giessen, Germany. Electronic address: christian.heiss@chiru.med.uni-giessen.de.
Jazyk:	angličtina
Zdroj:	The American journal of pathology [Am J Pathol] 2017 Aug; Vol. 187 (8), pp. 1686-1699. Date of Electronic Publication: 2017 Jun 12.
DOI:	10.1016/j.ajpath.2017.04.005
Abstrakt:	Osteoporosis induction in a sheep model by steroid administration combined with ovariectomy recapitulates decreased bone formation and substandard matrix mineralization in patients. Recently, the role of osteocytes has been frequently addressed, with focus on their role in osteoclastogenesis. However, the quantification of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) signaling in osteocytes was not studied in sheep. The current study reproduced the sheep model of osteoporosis to study the RANKL/OPG ratio correlation to the method of osteoporosis induction. We investigated the induction of osteoporosis after 8 months using 31 female merino land sheep divided into four groups: control, ovariectomy, ovariectomy with dietary limitation, and ovariectomy with dietary limitation and steroid injection. In accordance to previous reports, the present study showed trabecular thinning, higher numbers of apoptotic osteocytes, and imbalanced metabolism, leading to defective mineralization. The global RANKL/OPG ratio in the spine after 8 months of steroid and dietary treatment was not different from that of the control. Interestingly, assessment of the osteocyte-specific RANKL/OPG ratio showed that the steroid-induced osteoporosis in its late progressive phase stimulates RANKL expression in osteocytes. Sclerostin is suggested to induce RANKL expression in osteocytes. The findings of this study can contribute to further explain the success of sclerostin antibodies in treating osteoporotic patients despite increased osteocyte-expressed RANKL. (Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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