Research Paper Volume 11, Issue 17 pp 6983—6998

Curcumin suppresses osteogenesis by inducing miR-126a-3p and subsequently suppressing the WNT/LRP6 pathway

Hongling Li 1, *, , Lifeng Yue 2, *, , Haoying Xu 1, , Na Li 1, , Jing Li 1, , Zhiguo Zhang 3, , Robert Chunhua Zhao 1, ,

  • 1 Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy, Beijing 100005, China
  • 2 Beijing Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
  • 3 Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China
* Equal contribution

received: July 21, 2019 ; accepted: August 18, 2019 ; published: September 3, 2019 ;

https://doi.org/10.18632/aging.102232
How to Cite

Copyright © 2019 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Curcumin, a natural phenolic biphenyl compound derived from the plant Curcuma longa, modulates multiple steps of carcinogenesis partly by affecting the expression of miRNAs. Interestingly, cancer development shares many of the same signalling pathways with bone formation. Reduced bone mass creates favourable conditions for tumor metastasis. However, the effects and mechanism of curcumin on bone formation and osteogenesis are relatively unknown and controversial. We demonstrated that curcumin inhibited osteogenesis of human adipose-derived mesenchymal stem cells (hADSCs) in a concentration-dependent manner. In hADSCs, curcumin modulates the expression of a series of miRNAs, including miR-126a-3p, during osteogenesis. Overexpression or inhibition of miR-126a-3p is required for the effect of curcumin on osteogenesis. Further investigation indicated that miR-126a-3p directly targets and inhibits LRP6 through binding to its 3’-UTR, and then blocks WNT activation. Our findings suggest that the use of curcumin as an anti-tumor agent may lead to decreased bone mass through the suppression of osteogenesis. Knowing whether the long-term or high doses use of curcumin will cause decreased bone mass and bone density, which might increase the potential threat of tumor metastasis, also requires a neutral assessment of the role of curcumin in both regulating bone formation and bone absorption.

Abbreviations

hADSCs: human adipose-derived mesenchymal stem cells; 3́UTR: untranslated region; RUNX2: runt-related transcription factor; OSX: osterix; ALP: alkaline phosphatase; OPN: osteopontin; IBSP: integrin binding sialoprotein; LRP6: low-density lipoprotein receptor-related protein 6.