MMP and TIMP temporal gene expression during osteocytogenesis

Prideaux, M., Staines, K.A., Jones, Eleanor, Riley, Graham, Pitsillides, A and Farquharson, C (2015) MMP and TIMP temporal gene expression during osteocytogenesis. Gene Expression Patterns, 18 (1-2). 29–36. ISSN 1872-7298

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Abstract

Osteocytes within bone differentiate from osteoblast precursors which reside in a mineralised extracellular matrix (ECM). Fully differentiated osteocytes are critical for bone development and function but the factors that regulate this differentiation process are unknown. The enzymes primarily responsible for ECM remodelling are matrix metalloproteinases (MMP); however, the expression and role of MMPs during osteocytogenesis is undefined. Here we used MLO-A5 cells to determine the temporal gene expressions of the MMP family and their endogenous inhibitors – tissue inhibitors of metalloproteinases (TIMPs) during osteocytogenesis. RT-qPCR revealed expression of 14 Mmps and 3 Timps in MLO-A5 cells. Mmp2, Mmp23 and Mmp28 were decreased concurrent with mineralisation onset (P < 0.05*). Mmp14 and Mmp19 mRNAs were also significantly increased at day 3 (P < 0.05*) before returning to baseline levels at day 6. Decreased expressions of Timp1, Timp2 and Timp3 mRNA were observed by day 6 compared to day 0 (P < 0.05*). To examine whether these changes are linked to osteocytogenesis, we determined Mmp/Timp mRNA expressions in mineralisation-limited conditions. RT-qPCR revealed that the previously observed decreases in Mmp2, Mmp23 and Mmp28 were not observed in these mineralisation-limited cultures, therefore closely linking these MMPs with osteocyte differentiation. Similarly, we found differential expression of Timp1, Timp2 and Timp3 mRNA in mineralisation-restricted cultures (P < 0.05*). In conclusion, we have identified several members of the MMP/TIMP families as regulators of ECM remodelling necessary for the acquisition of the osteocyte phenotype.

Item Type:	Article
Uncontrolled Keywords:	osteocyte,mineralisation,mmp,timp,osteoblast
Faculty \ School:	Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine Faculty of Science > Research Groups > Cells and Tissues
Depositing User:	Pure Connector
Date Deposited:	06 Oct 2015 00:03
Last Modified:	15 Jul 2025 14:31
URI:	https://ueaeprints.uea.ac.uk/id/eprint/54359
DOI:	10.1016/j.gep.2015.04.004

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