The role of MKP-1 in the anti-proliferative effects of glucocorticoids in primary rat pre-osteoblasts

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dc.contributor.authorSanderson, Michelineen_ZA
dc.contributor.authorSadie-Van Gijsen, Hanelen_ZA
dc.contributor.authorHough, Stephenen_ZA
dc.contributor.authorFerris, William F.en_ZA
dc.date.accessioned2016-08-29T07:32:45Z
dc.date.available2016-08-29T07:32:45Z
dc.date.issued2015
dc.descriptionCITATION: Sanderson, M., et al. 2015. The role of MKP-1 in the anti-proliferative effects of glucocorticoids in primary rat pre-osteoblasts. PLoS ONE, 10(8):1-19, doi:10.1371/journal.pone.0135358.
dc.descriptionThe original publication is available at http://journals.plos.org/plosone
dc.description.abstractGlucocorticoid (GC)-induced osteoporosis has been attributed to a GC-induced suppression of pre-osteoblast proliferation. Our previous work identified a critical role for mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) in mediating the anti-proliferative effects of GCs in immortalized pre-osteoblasts, but we subsequently found that MKP-1 null mice were not protected against the pathological effects of GCs on bone. In order to reconcile this discrepancy, we have assessed the effects of GCs on proliferation, activation of the MAPK ERK1/2 and MKP-1 expression in primary adipose-derived stromal cells (ADSCs) and ADSC-derived pre-osteoblasts (ADSC-OBs). ADSCs were isolated by means of collagenase digestion from adipose tissue biopsies harvested from adult male Wistar rats. ADSC-OBs were prepared by treating ADSCs with osteoblast differentiation media for 7 days. The effects of increasing concentrations of the GC dexamethasone on basal and mitogen-stimulated cell proliferation were quantified by tritiated thymidine incorporation. ERK1/2 activity was measured by Western blotting, while MKP-1 expression was quantified on both RNA and protein levels, using semi-quantitative real-time PCR and Western blotting, respectively. GCs were strongly anti-proliferative in both naïve ADSCs and ADSC-OBs, but had very little effect on mitogen-induced ERK1/2 activation and did not upregulate MKP-1 protein expression. These findings suggest that the anti-proliferative effects of GCs in primary ADSCs and ADSC-OBs in vitro do not require the inhibition of ERK1/2 activation by MKP-1, which is consistent with our in vivo findings in MKP-1 null mice.en_ZA
dc.description.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0135358
dc.description.versionPublisher's version
dc.format.extent19 pages
dc.identifier.citationSanderson, M., et al. 2015. The role of MKP-1 in the anti-proliferative effects of glucocorticoids in primary rat pre-osteoblasts. PLoS ONE, 10(8):1-19, doi:10.1371/journal.pone.0135358
dc.identifier.issn1932-6203 (online)
dc.identifier.otherdoi:10.1371/journal.pone.0135358
dc.identifier.urihttp://hdl.handle.net/10019.1/99495
dc.language.isoen_ZAen_ZA
dc.publisherPublic Library of Science
dc.rights.holderAuthors retain copyright
dc.subjectGlucocorticoidsen_ZA
dc.subjectMitogen-activated protein kinase phosphatase 1en_ZA
dc.subjectPreosteoblastsen_ZA
dc.subjectOsteoporosis -- Epidemiologyen_ZA
dc.subjectPhosphatase activity and expressionen_ZA
dc.titleThe role of MKP-1 in the anti-proliferative effects of glucocorticoids in primary rat pre-osteoblastsen_ZA
dc.typeArticleen_ZA
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