@article{Ahmad2022, 
author = {Mubashir Ahmad and Benjamin Thilo Krüger and Torsten Kroll and Sabine Vettorazzi and Ann-Kristin Dorn and Florian Mengele and Sooyeon Lee and Sayantan Nandi and Dilay Yilmaz and Miriam Stolz and Naveen Kumar Tangudu and David Carro Vázquez and Johanna Pachmayr and Ion Cristian Cirstea and Maja Vujic Spasic and Aspasia Ploubidou and Anita Ignatius and Jan Tuckermann},
title = {Inhibition of Cdk5 increases osteoblast differentiation and bone mass and improves fracture healing},
year = {2022},
journal = {Bone Research},
volume = {10},
pages = {33},
url = {https://www.sciopen.com/article/10.1038/s41413-022-00195-z},
doi = {10.1038/s41413-022-00195-z},
abstract = {Identification of regulators of osteoblastogenesis that can be pharmacologically targeted is a major goal in combating osteoporosis, a common disease of the elderly population. Here, unbiased kinome RNAi screening in primary murine osteoblasts identified cyclin-dependent kinase 5 (Cdk5) as a suppressor of osteoblast differentiation in both murine and human preosteoblastic cells. Cdk5 knockdown by siRNA, genetic deletion using the Cre-loxP system, or inhibition with the small molecule roscovitine enhanced osteoblastogenesis in vitro. Roscovitine treatment significantly enhanced bone mass by increasing osteoblastogenesis and improved fracture healing in mice. Mechanistically, downregulation of Cdk5 expression increased Erk phosphorylation, resulting in enhanced osteoblast-specific gene expression. Notably, simultaneous Cdk5 and Erk depletion abrogated the osteoblastogenesis conferred by Cdk5 depletion alone, suggesting that Cdk5 regulates osteoblast differentiation through MAPK pathway modulation. We conclude that Cdk5 is a potential therapeutic target to treat osteoporosis and improve fracture healing.}
}