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Uncarboxylated osteocalcin promotes osteogenesis and inhibits adipogenesis of mouse bone marrow‑derived mesenchymal stem cells via the PKA‑AMPK‑SIRT1 axis

  • Authors:
    • Le Gao
    • Fang-Zi Gong
    • Lu-Yao Ma
    • Jian-Hong Yang
  • View Affiliations / Copyright

    Affiliations: Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, P.R. China
    Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 880
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    Published online on: June 15, 2021
       https://doi.org/10.3892/etm.2021.10312
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Abstract

Osteoporosis is a bone disease characterized by reduced bone density, thin cortical bone and large gaps in the bone's honeycomb structure, which increases the risk of bone fragility. Uncarboxylated osteocalcin (unOC), a vitamin K‑dependent bone protein, is known to regulate carbohydrate and energy metabolism. A previous study demonstrated that unOC promotes the differentiation of mouse bone marrow‑derived mesenchymal stem cells (BMSCs) into osteoblasts, but inhibits their differentiation into adipocytes. However, the underlying mechanism remains unknown. The present study showed that unOC regulated the differentiation potential of BMSCs via protein kinase A (PKA)/AMP‑activated protein kinase (AMPK)/sirtuin 1 (SIRT1) signaling. SIRT1, a member of the sirtuin family with deacetylation functions, was upregulated by unOC in BMSCs. Transfection analyses with SIRT1 small interfering RNA indicated that the unOC‑induced differentiation shift in BMSCs required SIRT1. Examination of SIRT1 downstream targets revealed that unOC regulated the acetylation levels of runt‑related transcription factor (RUNX) 2 and peroxisome proliferator‑activated receptor γ (PPARγ). Therefore, unOC inhibited adipogenic differentiation by PPARγ acetylation and promoted osteogenic differentiation by RUNX2 deacetylation. Moreover, phosphorylated PKA and AMPK protein levels increased after unOC treatment, which led to the upregulation of SIRT1. Western blot analysis with PKA and AMPK inhibitors indicated that the PKA‑AMPK signaling pathway functioned upstream of SIRT1 and positively regulated SIRT1 expression. These findings led us to propose a model in which unOC regulated BMSC osteogenic differentiation through the PKA‑AMPK‑SIRT1 axis, giving evidence towards the therapeutic potential of unOC in osteoporosis treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Gao L, Gong F, Ma L and Yang J: Uncarboxylated osteocalcin promotes osteogenesis and inhibits adipogenesis of mouse bone marrow‑derived mesenchymal stem cells via the PKA‑AMPK‑SIRT1 axis. Exp Ther Med 22: 880, 2021.
APA
Gao, L., Gong, F., Ma, L., & Yang, J. (2021). Uncarboxylated osteocalcin promotes osteogenesis and inhibits adipogenesis of mouse bone marrow‑derived mesenchymal stem cells via the PKA‑AMPK‑SIRT1 axis. Experimental and Therapeutic Medicine, 22, 880. https://doi.org/10.3892/etm.2021.10312
MLA
Gao, L., Gong, F., Ma, L., Yang, J."Uncarboxylated osteocalcin promotes osteogenesis and inhibits adipogenesis of mouse bone marrow‑derived mesenchymal stem cells via the PKA‑AMPK‑SIRT1 axis". Experimental and Therapeutic Medicine 22.2 (2021): 880.
Chicago
Gao, L., Gong, F., Ma, L., Yang, J."Uncarboxylated osteocalcin promotes osteogenesis and inhibits adipogenesis of mouse bone marrow‑derived mesenchymal stem cells via the PKA‑AMPK‑SIRT1 axis". Experimental and Therapeutic Medicine 22, no. 2 (2021): 880. https://doi.org/10.3892/etm.2021.10312
Copy and paste a formatted citation
x
Spandidos Publications style
Gao L, Gong F, Ma L and Yang J: Uncarboxylated osteocalcin promotes osteogenesis and inhibits adipogenesis of mouse bone marrow‑derived mesenchymal stem cells via the PKA‑AMPK‑SIRT1 axis. Exp Ther Med 22: 880, 2021.
APA
Gao, L., Gong, F., Ma, L., & Yang, J. (2021). Uncarboxylated osteocalcin promotes osteogenesis and inhibits adipogenesis of mouse bone marrow‑derived mesenchymal stem cells via the PKA‑AMPK‑SIRT1 axis. Experimental and Therapeutic Medicine, 22, 880. https://doi.org/10.3892/etm.2021.10312
MLA
Gao, L., Gong, F., Ma, L., Yang, J."Uncarboxylated osteocalcin promotes osteogenesis and inhibits adipogenesis of mouse bone marrow‑derived mesenchymal stem cells via the PKA‑AMPK‑SIRT1 axis". Experimental and Therapeutic Medicine 22.2 (2021): 880.
Chicago
Gao, L., Gong, F., Ma, L., Yang, J."Uncarboxylated osteocalcin promotes osteogenesis and inhibits adipogenesis of mouse bone marrow‑derived mesenchymal stem cells via the PKA‑AMPK‑SIRT1 axis". Experimental and Therapeutic Medicine 22, no. 2 (2021): 880. https://doi.org/10.3892/etm.2021.10312
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