The Inhibitors of Cyclin-dependent Kinases and GSK-3β Enhance Osteoclastogenesis

Overview

Journal Biochem Biophys Rep

Specialty Biochemistry

Date 2017 Sep 29

PMID 28955831

Citations 3

Authors

Yosuke Akiba

Akiko Mizuta

Yoshito Kakihara

Juri Nakata

Jun Nihara

Isao Saito

Hiroshi Egusa

Makio Saeki

Affiliations

Soon will be listed here.

Abstract

Osteoclasts are multinucleated cells with bone resorption activity that is crucial for bone remodeling. RANK-RANKL (receptor activator of nuclear factor κB ligand) signaling has been shown as a main signal pathway for osteoclast differentiation. However, the molecular mechanism and the factors regulating osteoclastogenesis remain to be fully understood. In this study, we performed a chemical genetic screen, and identified a Cdks/GSK-3β (cyclin-dependent kinases/glycogen synthase kinase 3β) inhibitor, kenpaullone, and two Cdks inhibitors, olomoucine and roscovitine, all of which significantly enhance osteoclastogenesis of RAW264.7 cells by upregulating NFATc1 (nuclear factor of activated T cells, cytoplasmic 1) levels. We also determined that the all three compounds increase the number of osteoclast differentiated from murine bone marrow cells. Furthermore, the three inhibitors, especially kenpaullone, promoted maturation of cathepsin K, suggesting that the resorption activity of the resultant osteoclasts is also activated. Our findings indicate that inhibition of GSK-3β and/or Cdks enhance osteoclastogenesis by modulating the RANK-RANKL signaling pathway.

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