| First Author | Yamada T | Year | 2022 |
| Journal | Stem Cell Reports | Volume | 17 |
| Issue | 7 | Pages | 1576-1588 |
| PubMed ID | 35777359 | Mgi Jnum | J:328686 |
| Mgi Id | MGI:7316101 | Doi | 10.1016/j.stemcr.2022.06.001 |
| Citation | Yamada T, et al. (2022) The role of CDK8 in mesenchymal stem cells in controlling osteoclastogenesis and bone homeostasis. Stem Cell Reports 17(7):1576-1588 |
| abstractText | Bone marrow mesenchymal stem cells (MSCs) are critical regulators of postnatal bone homeostasis. Osteoporosis is characterized by bone volume and strength deterioration, partly due to MSC dysfunction. Cyclin-dependent kinase 8 (CDK8) belongs to the transcription-related CDK family. Here, CDK8 in MSCs was identified as important for bone homeostasis. CDK8 level was increased in aged MSCs along with the association with aging-related signals. Mouse genetic studies revealed that CDK8 in MSCs plays a crucial role in bone resorption and homeostasis. Mechanistically, CDK8 in MSCs extrinsically controls osteoclastogenesis through the signal transducer and transcription 1 (STAT1)-receptor activator of the nuclear factor kappa Beta ligand (RANKL) axis. Moreover, aged MSCs have high osteoclastogenesis-supporting activity, partly through a CDK8-dependent manner. Finally, pharmacological inhibition of CDK8 effectively repressed MSC-dependent osteoclastogenesis and prevented ovariectomy-induced osteoclastic activation and bone loss. These findings highlight that the CDK8-STAT1-RANKL axis in MSCs could play a crucial role in bone resorption and homeostasis. |
