Dual targeting of salt inducible kinases and CSF1R uncouples bone formation and bone resorption.
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ABSTRACT:
SUBMITTER: Tang CC
PROVIDER: S-EPMC8238509 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
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Dual targeting of salt inducible kinases and CSF1R uncouples bone formation and bone resorption.
Tang Cheng-Chia CC Castro Andrade Christian D CD O'Meara Maureen J MJ Yoon Sung-Hee SH Sato Tadatoshi T Brooks Daniel J DJ Bouxsein Mary L ML Martins Janaina da Silva JDS Wang Jinhua J Gray Nathanael S NS Misof Barbara B Roschger Paul P Blouin Stephane S Klaushofer Klaus K Velduis-Vlug Annegreet A Vegting Yosta Y Rosen Clifford J CJ O'Connell Daniel D Sundberg Thomas B TB Xavier Ramnik J RJ Ung Peter P Schlessinger Avner A Kronenberg Henry M HM Berdeaux Rebecca R Foretz Marc M Wein Marc N MN
eLife 20210623
Bone formation and resorption are typically coupled, such that the efficacy of anabolic osteoporosis treatments may be limited by bone destruction. The multi-kinase inhibitor YKL-05-099 potently inhibits salt inducible kinases (SIKs) and may represent a promising new class of bone anabolic agents. Here, we report that YKL-05-099 increases bone formation in hypogonadal female mice without increasing bone resorption. Postnatal mice with inducible, global deletion of SIK2 and SIK3 show increased bo ...[more]
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