Quercetin prevents bone loss in hindlimb suspension mice via stanniocalcin 1-mediated inhibition of osteoclastogenesis

Yin-bo Niu1, Yuan-yuan Yang1, Xuan Xiao1,2, Yang Sun3, Yu-mei Zhou3, Yu-han Zhang1, Dong Dong1, Chen-rui Li1, Xiang-long Wu1, Yu-hua Li4, Qi-bing Mei1,4
1 Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China
2 Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China
3 Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi’an 710032, China
4 Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China
Correspondence to: Yu-hua Li:, Qi-bing Mei:,
DOI: 10.1038/s41401-020-00509-z
Received: 15 May 2020
Accepted: 16 August 2020
Advance online: 15 September 2020


Recent studies demonstrate that diet quercetin (Quer) has obvious bone protective effects on ovariectomized rodents but thus far there is no direct evidence to support the inhibitory effect of Quer on bone loss caused by long-term unloading. In the present study, we investigated whether Quer could prevent bone loss induced by unloading in mice. Mice were subjected to hindlimb suspension (HLS) and received Quer (25, 50, 100 mg· kg−1 ·day−1, ig) for 4 weeks. Before euthanasia blood sample was collected; the femurs were harvested and subjected to MicroCT analysis. We showed that Quer administration markedly improved bone microstructure evidenced by dose-dependently reversing the reduction in bone volume per tissue volume, trabecular number, and bone mineral density, and the increase of trabecular spacing in mice with HLS. Analysis of serum markers and bone histometric parameters confirmed that Quer at both middle and high doses significantly decreased bone resorption-related markers collagen type I and tartrate-resistant acid phosphatase 5b, and increased bone formation-related marker procollagen 1 N-terminal propeptide as compared with HLS group. Treatment with Quer (1, 2, 5 μM) dose-dependently inhibited RANKL-induced osteoclastogenesis through promoting the expression of antioxidant hormone stanniocalcin 1 (STC1) and decreasing ROS generation; knockdown of STC1 blocked the inhibitory effect of Quer on ROS generation. Knockdown of STC1 also significantly promoted osteoclastogenesis in primary osteoclasts. In conclusion, Quer protects bones and prevents unloading-caused bone loss in mice through STC1-mediated inhibition of osteoclastogenesis. The findings suggest that Quer has the potential to prevent and treat off-load bone loss as an alternative supplement.
Keywords: quercetin; bone loss; osteoclast; STC1; ROS; hindlimb suspension mice

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