JEM: regulation of microtubule binding protein dcamkl1 found in biochemistry and cell

On August 5, the Journal of Experimental Medicine published online a research paper entitled microtubule associated protein dcamkl1 regulations osteoblast function via expression of Runx2 by Zou Weiguo research group, Shanghai Institute of Biochemistry and cell biology, Chinese Academy of Sciences This study found that dcamkl1 regulated the function of osteoblasts by inhibiting the activity of transcription factor Runx2 The growth, development and metabolism of bone are important life activities of the body Osteoblasts come from mesodermal mesenchymal stem cells, which can secrete bone matrix and mineralize it to form new bone structure In this study, the slow virus based shRNA library was introduced into the primary cultured mesenchymal stem cells, and then induced to differentiate into osteoblasts The activity of alkaline phosphatase, an early marker of differentiation, was quantitatively detected, and the new regulatory factors of osteoblasts differentiation were screened by high throughput It was found that the ability of MSCs to differentiate into osteoblasts was enhanced when dcamkl1 was knocked down The function of osteoblasts, the rate of bone formation and the density of bone were increased in dcankl1 knockout mice The study of molecular mechanism shows that dcamkl1 can inhibit the activity of Runx2, the main transcription factor of osteoblast differentiation, by increasing the aggregation of tubulin A variety of mutations in Runx2 result in human autosomal dominant disease, clavicular dysplasia (CCD), which is characterized by clavicular dysplasia and persistent craniotomy In accordance with this, Runx2 heterozygous mice also showed clavicular and cranial hypoplasia All these CCD related phenotypes could be partially recovered by gene knockout of dcamkl1, which further confirmed the genetic relationship between dcamkl1 and Runx2 This study established a method of screening new regulatory factors in osteoblasts by using the positive genetic method, identified a new regulatory factor regulating the function of osteoblasts, suggesting that bone strength may be enhanced by regulating the aggregation of microtubules, so as to treat osteoporosis and other diseases The work started from researcher Zou Weiguo's work abroad and was jointly completed by researchers from Institute of Biochemistry and cell biology, Chinese Academy of Sciences, Harvard University Medical School, Cornell University, Harvard University School of Stomatology and Merck company Researcher Zou Weiguo is the first author and corresponding author of the article The work was supported by the start-up fund of Institute of Biochemistry and cell biology, Chinese Academy of Sciences, the fund of National Key Laboratory of cell biology and NIH project.