Mechanisms of mitogen-activated protein kinase inhibition by parathyroid hormone in osteoblast-like cells
In: Journal of the American Society of Nephrology, Jg. 15 (2004), Heft 11, S. 2844-2850
academicJournal
- print, 24 ref
Zugriff:
Parathyroid hormone (PTH) dose dependently inhibits growth factor- and stress-induced osteoblast proliferation via inactivating mitogen-activated protein kinase (MAPK) signaling pathways. Osteoblasts have recently been shown to express MAPK phosphatase (MKP)-1, a dual-specific phosphatase inactivator of MAPK. Investigated was the role of MKPs in the PTH-induced attenuation of MAPK and Jun N-terminal kinase (JNK) signaling in osteoblast-like UMR106-01 cells. PTH induced a persistent inhibition of p42/44 MAPK and JNK phosphorylation starting at 10 min of incubation and lasting for at least 2 h. Actinomycin D affected both p42/44 MAPK and JNK dephosphorylation by PTH, suggesting a transcription-dependent mechanism of action. PTH rapidly and transiently induced expression of MKP-1. MKP-1 mRNA was already elevated after 10 min of 10-7 M PTH incubation, reached maximal expression after 30 to 60 min, and remained elevated after 4 h. MKP-1 protein was also upregulated within 30 to 60 min of PTH administration. The protein kinase A inhibitor H89 partly reduced PTH-induced MKP-1 expression, but the protein kinase C inhibitor bisindolylmaleimide had no effect, suggesting that PTH induces MKP- 1 mainly via the protein kinase A pathway. MKP-2 mRNA was downregulated after 2 h after an early period of induction, and MKP-3 mRNA was immediately reduced. Ro 318-220 did not affect PTH-induced MAPK inactivation but effectively blocked JNK dephosphorylation. The time course of PTH-induced MKP-I protein expression closely correlated with JNK dephosphorylation. PTH attenuates the stress-induced JNK signaling pathway in osteoblasts via induction of MKP-1 synthesis but inhibits the p42/44 MAPK pathway mainly via transcription-independent mechanisms.
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Mechanisms of mitogen-activated protein kinase inhibition by parathyroid hormone in osteoblast-like cells
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Autor/in / Beteiligte Person: | HÖMME, Meike ; SCHMITT, Claus P ; MEHLS, Otto ; SCHAEFER, Franz |
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Zeitschrift: | Journal of the American Society of Nephrology, Jg. 15 (2004), Heft 11, S. 2844-2850 |
Veröffentlichung: | Hagerstown, MD: Lippincott Williams & Wilkins, 2004 |
Medientyp: | academicJournal |
Umfang: | print, 24 ref |
ISSN: | 1046-6673 (print) |
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