Document Detail


MKP1-dependent PTH modulation of bone matrix mineralization in female mice is osteoblast maturation stage specific and involves P-ERK and P-p38 MAPKs.
MedLine Citation:
PMID:  23197743     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Limited information is available on the role of MAPK phosphatase 1 (MKP1) signaling in osteoblasts. We have recently reported distinct roles for MKP1 during osteoblast proliferation, differentiation, and skeletal responsiveness to parathyroid hormone (PTH). As MKP1 regulates the phosphorylation status of MAPKs, we investigated the involvement of P-ERK and P-p38 MAPKs in MKP1 knockout (KO) early and mature osteoblasts with respect to mineralization and PTH response. Calvarial osteoblasts from 9-14-week-old WT and MKP1 KO male and female mice were examined. Western blot analysis revealed downregulation and sustained expressions of P-ERK and P-p38 with PTH treatment in differentiated osteoblasts derived from KO males and females respectively. Exposure of early osteoblasts to p38 inhibitor, SB203580 (S), markedly inhibited mineralization in WT and KO osteoblasts from both genders as determined by von Kossa assay. In osteoblasts from males, ERK inhibitor U0126 (U), not p38 inhibitor (S), prevented the inhibitory effects of PTH on mineralization in early or mature osteoblasts. In osteoblasts from KO females, PTH sustained mineralization in early osteoblasts and decreased mineralization in mature cells. This effect of PTH was attenuated by S in early osteoblasts and by U in mature KO cells. Changes in matrix Gla protein expression with PTH in KO osteoblasts did not correlate with mineralization, indicative of MKP1-dependent additional mechanisms essential for PTH action on osteoblast mineralization. We conclude that PTH regulation of osteoblast mineralization in female mice is maturation stage specific and involves MKP1 modulation of P-ERK and P-p38 MAPKs.
Authors:
Chandrika D Mahalingam; Bharat Reddy Sampathi; Sonali Sharma; Tanuka Datta; Varsha Das; Abdul B Abou-Samra; Nabanita S Datta
Related Documents :
9539223 - Involvement of phosphatase activities in the run-down of gaba(a) receptor function in r...
8772443 - Shrinkage activates a nonselective conductance: involvement of a walker-motif protein a...
11459643 - Phytoestrogens from the roots of polygonum cuspidatum (polygonaceae): structure-require...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-02-25
Journal Detail:
Title:  The Journal of endocrinology     Volume:  216     ISSN:  1479-6805     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-26     Completed Date:  2013-04-30     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  315-29     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Butadienes / pharmacology
Calcification, Physiologic / drug effects,  physiology*
Cell Differentiation / drug effects
Down-Regulation
Dual Specificity Phosphatase 1 / genetics,  metabolism*
Enzyme Inhibitors / pharmacology
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors,  metabolism*
Female
Imidazoles / pharmacology
Male
Mice
Mice, Knockout
Nitriles / pharmacology
Osteoblasts / drug effects,  metabolism*
Parathyroid Hormone / pharmacology*
Phosphorylation / drug effects,  physiology
Pyridines / pharmacology
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism*
Grant Support
ID/Acronym/Agency:
DK087848/DK/NIDDK NIH HHS; R56 DK087848/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Butadienes; 0/Enzyme Inhibitors; 0/Imidazoles; 0/Nitriles; 0/Parathyroid Hormone; 0/Pyridines; 0/SB 203580; 0/U 0126; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.1.3.48/Dual Specificity Phosphatase 1
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Repetitive magnetic stimulation induces functional and structural plasticity of excitatory postsynap...
Next Document:  Role of human chorionic gonadotropin in regulation of gastric emptying in ovariectomized rats.