Download This Paper
Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.
Curcumin Suppresses Osteogenesis by Inducing miR-126a-3p and Subsequently Suppressing the WNT/LRP6 Pathway
36 Pages Posted: 22 Jul 2019
More...Abstract
Background: Curcumin, a natural phenolic biphenyl compound derived from the plant Curcuma longa, modulates multiple steps of carcinogenesis, including inhibiting cell proliferation, induction of apoptosis, and amelioration of resistance to chemotherapeutic agents, 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.
Methods: Effects of curcumin on osteogenic differentiation were evaluated in human adipose-derived mesenchymal stem cells (hADSCs). Microarray analysis was used to detected relevant miRNA regulated by curcumin. By prediction and validation of the target genes, mechanism involved in curcumin-influenced osteogenesis was examined.
Findings: Curcumin inhibited osteogenesis of hADSCs in a concentration-dependent manner. In hADSCs, curcumin modulates the expression of a series of miRNAs, including miR126a-3p. Overexpression or inhibition of miR126a-3p is required for the effect of curcumin on osteogenesis. Further investigation indicated that miR-126a directly targets and inhibits LRP6 through binding to its 3'-UTR, and then blocks WNT activation.
Interpretation: 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.
Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (No. 81700782, 81473450, 81302960, 81672313), Top Young Scientist Funds and Top Young Doctor Funds of Beijing University of Chinese Medicine (No. BUCM-2019-JCRC007, BUCM-2019-QNMYB011), the National Key Research and Development Program of China (2016YFA0101000, 2016YFA0101003, 2018YFA0109800), the Fundamental Research Funds for the Central Public Welfare Research Institutes (YZ-1780), the 111 Project (B18007), the key technologies R&D program of Sichuan Province (2015SZ0020), and the CAMS Innovation Fund for Medical Sciences (2017-I2M-3-007).
Declaration of Interests: The authors declare no conflicts of interest.
Ethics Approval Statement: Human adipose tissue was obtained from patients undergoing tumescent liposuction according to procedures approved by the Ethics Committee at the Chinese Academy of Medical Sciences and Peking Union Medical College.
Keywords: Curcumin; miR-126a; mesenchymal stem cells; osteogenesis; LRP6
Suggested Citation: Suggested Citation