Open Access

gCTRP3 inhibits oophorectomy‑induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway in mice

  • Authors:
    • Xiaojuan Zhang
    • Di Zhang
    • Huan Zhao
    • Jing Qin
    • Hao Qi
    • Feiyu Zu
    • Yaru Zhou
    • Yingze Zhang
  • View Affiliations

  • Published online on: May 28, 2024     https://doi.org/10.3892/mmr.2024.13257
  • Article Number: 133
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

C1q/tumor necrosis factor‑related protein 3 (CTRP3) expression is markedly reduced in the serum of patients with osteoporosis. The present study aimed to investigate whether CTRP3 reduces bone loss in oophorectomy (OVX)‑induced mice via the AMP‑activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/nuclear factor E2‑related factor 2 (Nrf2) signaling pathway. Female C57BL/6J mice and MC3T3‑E1 cells were used to construct in vivo and in vitro models of osteoporosis, respectively. The left femurs of mice were examined using micro‑computed tomography scans and bone‑related quantitative morphological evaluation was performed. Pathological changes and the number of osteoclasts in the left femurs of mice were detected using hematoxylin and eosin, and tartrate‑resistant acid phosphatase (TRAP) staining. Runt‑related transcription factor‑2 (RUNX2) expression in the left femurs was detected using immunofluorescence analysis, and the serum levels of bone resorption markers (C‑telopeptide of type I collagen and TRAP) and bone formation markers [osteocalcin (OCN) and procollagen type 1 N‑terminal propeptide] were detected. In addition, osteoblast differentiation and calcium deposits were examined in MC3T3‑E1 cells using alkaline phosphatase (ALP) and Alizarin red staining, respectively. Moreover, RUNX2, ALP and OCN expression levels were detected using reverse transcription‑quantitative PCR, and the expression levels of proteins associated with the AMPK/SIRT1/Nrf2 signaling pathway were detected using western blot analysis. The results revealed that globular CTRP3 (gCTRP3) alleviated bone loss and promoted bone formation in OVX‑induced mice. gCTRP3 also facilitated the osteogenic differentiation of MC3T3‑E1 cells through the AMPK/SIRT1/Nrf2 signaling pathway. The addition of an AMPK inhibitor (Compound C), SIRT1 inhibitor (EX527) or Nrf2 inhibitor (ML385) reduced the osteogenic differentiation of MC3T3‑E1 cells via inhibition of gCTRP3. In conclusion, gCTRP3 inhibits OVX‑induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway.
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August-2024
Volume 30 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Zhang X, Zhang D, Zhao H, Qin J, Qi H, Zu F, Zhou Y and Zhang Y: gCTRP3 inhibits oophorectomy‑induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway in mice. Mol Med Rep 30: 133, 2024.
APA
Zhang, X., Zhang, D., Zhao, H., Qin, J., Qi, H., Zu, F. ... Zhang, Y. (2024). gCTRP3 inhibits oophorectomy‑induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway in mice. Molecular Medicine Reports, 30, 133. https://doi.org/10.3892/mmr.2024.13257
MLA
Zhang, X., Zhang, D., Zhao, H., Qin, J., Qi, H., Zu, F., Zhou, Y., Zhang, Y."gCTRP3 inhibits oophorectomy‑induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway in mice". Molecular Medicine Reports 30.2 (2024): 133.
Chicago
Zhang, X., Zhang, D., Zhao, H., Qin, J., Qi, H., Zu, F., Zhou, Y., Zhang, Y."gCTRP3 inhibits oophorectomy‑induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway in mice". Molecular Medicine Reports 30, no. 2 (2024): 133. https://doi.org/10.3892/mmr.2024.13257