MKP-1 knockout does not prevent glucocorticoid-induced bone disease in mice.

Conradie, M; Cato, A; Ferris, W; De Wet, H; Horsch, K; Hough, S

Journal article

MKP-1 knockout does not prevent glucocorticoid-induced bone disease in mice.

Abstract:: Glucocorticoid-induced osteoporosis (GCOP) is predominantly caused by inhibition of bone formation, resulting from a decrease in osteoblast numbers. Employing mouse (MBA-15.4) and human (MG-63) osteoblast cell lines, we previously found that the glucocorticoid (GC) dexamethasone (Dex) inhibits cellular proliferation as well as activation of the MAPK/ERK signaling pathway, essential for mitogenesis in these cells, and that both these effects could be reversed by the protein tyrosine phosphatase (PTP) inhibitor vanadate. In a rat model of GCOP, the GC-induced changes in bone formation, mass, and strength could be prevented by vanadate cotreatment, suggesting that the GC effects on bone were mediated by one or more PTPs. Employing phosphatase inhibitors, qRT-PCR, Western blotting, and overexpression/knockdown experiments, we concluded that MKP-1 was upregulated by Dex, that this correlated with the dephosphorylation of ERK, and that it largely mediated the in vitro effects of GCs on bone. To confirm the pivotal role of MKP-1 in vivo, we investigated the effects of the GC methylprednisolone on the quantitative bone histology of wild-type (WT) and MKP-1 homozygous knockout (MKP-1(-/-)) mice. In WT mice, static bone histology revealed that GC administration for 28 days decreased osteoid surfaces, volumes, and osteoblast numbers. Dynamic histology, following time-spaced tetracycline labeling, confirmed a significant GC-induced reduction in osteoblast appositional rate and bone formation rate. However, identical results were obtained in MKP-1 knockout mice, suggesting that in these animals upregulation of MKP-1 by GCs cannot be regarded as the sole mediator of the GC effects on bone.

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APA Style

Conradie, M., Cato, A., Ferris, W., De Wet, H., Horsch, K., & Hough, S. (2011). MKP-1 knockout does not prevent glucocorticoid-induced bone disease in mice. Calcified Tissue International, 89(3), 221–227.

MLA Style

Conradie, M., et al. “MKP-1 Knockout Does Not Prevent Glucocorticoid-Induced Bone Disease in Mice.” Calcified Tissue International, vol. 89, no. 3, 2011, pp. 221–27.

Chicago Style

Conradie, M, A Cato, W Ferris, H De Wet, K Horsch, and S Hough. 2011. “MKP-1 Knockout Does Not Prevent Glucocorticoid-Induced Bone Disease in Mice.” Calcified Tissue International 89 (3): 221–27.
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