Sclerostin Antibody Augments the Anabolic Bone Formation Response in a Mouse Model of Mechanical Tibial Loading

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
A MorseD G Little

Abstract

Decreased activity or expression of sclerostin, an endogenous inhibitor of Wnt/β-catenin signaling, results in increased bone formation and mass. Antibodies targeting and neutralizing sclerostin (Scl-Ab) have been shown to increase bone mass and reduce fracture risk. Sclerostin is also important in modulating the response of bone to changes in its biomechanical environment. However, the effects of Scl-Ab on mechanotransduction are unclear, and it was speculated that the loading response may be altered for individuals receiving Scl-Ab therapy. To address this, we carried out a 2-week study of tibial cyclic compressive loading on C57Bl/6 mice treated with vehicle or 100 mg/kg/wk Scl-Ab. Increases in bone volume, density, and dynamic bone formation were found with loading, and the anabolic response was further increased by the combination of load and Scl-Ab. To investigate the underlying mechanism, gene profiling by RNA sequencing (RNAseq) was performed on tibias isolated from mice from all four experimental groups. Major alterations in Wnt/β-catenin gene expression were found with tibial loading, however not with Scl-Ab treatment alone. Notably, the combination of load and Scl-Ab elicited a synergistic response from a number of s...Continue Reading

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Citations

Nov 13, 2018·Journal of Cellular Physiology·Lufei WangHu Long
May 17, 2019·Current Osteoporosis Reports·Ugur Ayturk
May 31, 2018·Calcified Tissue International·Alyson MorseDavid G Little
May 28, 2019·JBMR Plus·Sundar SrinivasanTed S Gross
Oct 14, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Maude GerbaixSerge Ferrari
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Feb 23, 2021·JBMR Plus·Scott DillonColin Farquharson
Jul 3, 2021·International Journal of Molecular Sciences·Lanlan Zhang, Chunyi Wen
Aug 10, 2021·Frontiers in Pharmacology·Shan-Shan LiDai-Feng Li
Sep 22, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zilong YaoBin Yu

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