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

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.