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Rapamycin could increase the effects of melatonin against age-dependent bone loss

Rapamycin könnte die Wirkung von Melatonin gegen altersbedingten Knochenverlust verstärken

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Abstract

Previous studies have demonstrated the beneficial effect of melatonin (MEL) on bone tissue and bone metabolism. Rapamycin (RAP) promotes osteoblast proliferation and inhibits osteoclast proliferation, and positively affects bone regeneration; however, reports about effects of RAP on bone loss for aged female rats with MEL administration are limited. This study investigated the impact of treatment with RAP on bone loss for aged female rats with MEL administration. Female Sprague-Dawley rats weighing approximately 520 g were randomly divided into 3 groups of 10: group CON, group MEL and group MEL + RAP and received saline, MEL, RAP plus MEL treatment until death at 12 weeks, respectively. The results of maintaining bone mass and bone strength with RAP plus MEL administration were evaluated by histology, microcomputerized tomography (Micro-CT), gene expression analysis and biomechanical testing. Results from this study indicated that MEL + RAP had stronger effects on the prevention and treatment of osteoporosis than MEL administration. Administration of MEL + RAP produced the strongest effects on bone parameters and strength for distal femurs and regulation of OPG/RANKL signalling pathway-related gene expression. These results seemed to indicate that RAP could increase the effects of MEL on age-dependent bone loss.

Zusammenfassung

Frühere Studien haben die positive Wirkung von Melatonin (MEL) auf das Knochengewebe und den Knochenstoffwechsel gezeigt. Rapamycin (RAP) fördert die Osteoblastenproliferation, hemmt die Osteoklastenproliferation und wirkt sich positiv auf die Knochenregeneration aus. Berichte über die Auswirkungen von RAP auf den Knochenverlust bei älteren weiblichen Ratten mit MEL-Verabreichung sind jedoch begrenzt. Diese Studie untersuchte die Auswirkungen der RAP-Behandlung auf den Knochenabbau bei älteren weiblichen Ratten mit MEL-Gabe. Weibliche Sprague-Dawley-Ratten mit einem Gewicht von ca. 520 g wurden in 3 Gruppen randomisiert: Gruppe CON, Gruppe MEL und Gruppe MEL + RAP. Sie erhielten eine Behandlung mit entweder Kochsalzlösung, MEL- oder RAP plus MEL bis zum Tod nach 12 Wochen. Die Ergebnisse der Erhaltung der Knochenmasse und Knochenstärke mit der Verabreichung von MEL + RAP wurden durch Histologie, Mikro-Computertomographie (Mikro-CT), Genexpressionsanalyse und biomechanische Tests bewertet. Die Ergebnisse dieser Studie zeigten, dass MEL + RAP stärkere Auswirkungen auf die Prävention und Behandlung von Osteoporose hatte als die Gabe von MEL. Die Verabreichung von MEL + RAP hatte die stärksten Auswirkungen auf die Knochenparameter sowie die Festigkeit des distalen Femurs und die Regulation der OPG/RANKL-Signalweg-bezogenen Genexpression. Diese Ergebnisse schienen darauf hinzudeuten, dass RAP die Auswirkungen von MEL auf den altersbedingten Knochenabbau verstärken könnte.

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Funding

This study was supported by a grant from the University Natural Science Research Project of Anhui Province (CN) (grant no. KJ2017A266), and funding of Peak Training Program and Pan feng Innovation Team Project for Scientific Research of Yijishan Hospital, Wannan Medical College(grant nos. GF2019G04, PF2019005, GF2019T02 and PF2019007).

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Authors and Affiliations

  1. Department of Trauma Orthopedics, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, No. 2, Zhe shan Xi Road, 241001, Wuhu, Anhui, China

    Zhou-Shan Tao, Han-Li Lu, Neng-Feng Ma, Rou-Tian Zhang, Yang Li & Min Yang

  2. Spine Research Center of Wannan Medical College; Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution; Dept of Spine Surgery, Yijishan hospital of Wannan Medical College, No. 2, Zhe shan Xi Road, 241001, Wuhu, Anhui, China

    Hong-Guang Xu

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  1. Zhou-Shan Tao
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Correspondence to Min Yang or Hong-Guang Xu.

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Z.‑S. Tao, H.‑L. Lu, N.‑F. Ma, R.‑T. Zhang, Y. Li, M. Yang and H.‑G. Xu declare that they have no competing interests.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institutional and/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards.

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Tao, ZS., Lu, HL., Ma, NF. et al. Rapamycin could increase the effects of melatonin against age-dependent bone loss. Z Gerontol Geriat 53, 671–678 (2020). https://doi.org/10.1007/s00391-019-01659-4

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