Katherine Ann Staines
Identification of novel regulators of osteoblast matrix mineralization by time series transcriptional profiling
Staines, Katherine Ann; Zhu, Dongxing; Farquharson, Colin; MacRae, Vicky Elizabeth
Authors
Dongxing Zhu
Colin Farquharson
Vicky Elizabeth MacRae
Abstract
Bone mineralization is a carefully orchestrated process, regulated by a number of promoters and inhibitors that function to ensure effective hydroxyapatite formation. Here we sought to identify new regulators of this process through a time series microarray analysis of mineralising primary osteoblast cultures over a 27 day culture period. To our knowledge this is the first microarray study investigating murine calvarial osteoblasts cultured under conditions that permit both physiological extracellular matrix mineralization through the formation of discrete nodules and the terminal differentiation of osteoblasts into osteocytes. RT-qPCR was used to validate and expand the microarray findings. We demonstrate the significant up-regulation of >6,000 genes during the osteoblast mineralization process, the highest-ranked differentially expressed genes of which were those dominated by members of the PPAR-γ signalling pathway, namely Adipoq, Cd36 and Fabp4. Furthermore, we show that the inhibition of this signalling pathway promotes matrix mineralisation in these primary osteoblast cultures. We also identify Cilp, Phex, Trb3, Sox11, and Psat1 as novel regulators of matrix mineralization. Further studies examining the precise function of the identified genes and their interactions will advance our understanding of the mechanisms underpinning biomineralization.
Citation
Staines, K. A., Zhu, D., Farquharson, C., & MacRae, V. E. (2014). Identification of novel regulators of osteoblast matrix mineralization by time series transcriptional profiling. Journal of Bone and Mineral Metabolism, 32(3), 240-251. https://doi.org/10.1007/s00774-013-0493-2
| Journal Article Type | Article |
|---|---|
| Online Publication Date | Aug 8, 2013 |
| Publication Date | 2014-05 |
| Deposit Date | Jan 20, 2017 |
| Journal | Journal of Bone and Mineral Metabolism |
| Print ISSN | 0914-8779 |
| Electronic ISSN | 1435-5604 |
| Publisher | BMC |
| Peer Reviewed | Peer Reviewed |
| Volume | 32 |
| Issue | 3 |
| Pages | 240-251 |
| DOI | https://doi.org/10.1007/s00774-013-0493-2 |
| Keywords | Bone, Osteoblast, Mineralization, Microarray, PPAR-γ, |
| Public URL | http://researchrepository.napier.ac.uk/Output/466173 |