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Decreased mineralization and lack of cyclin D1 response to Parathyroid Hormone Related Peptide (PTHrP) in primary osteoblasts isolated from MKP‐1 knock out mice
Author(s) -
Datta Nabanita,
Chaker Bayan,
AbouSamra Abdul
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.858.1
Subject(s) - chemistry , endocrinology , medicine , osteoblast , anabolism , cyclin d1 , parathyroid hormone , alkaline phosphatase , mapk/erk pathway , in vitro , kinase , calcium , cell cycle , biochemistry , cell , enzyme
MAPK phosphatase 1 (MKP‐1), a member of the dual‐specificity phosphatases, inactivate MAPKs via dephosphorylation of ERK, p38 and JNK. Whether MKP‐1 plays a role in PTH and PTHrP anabolic action in bone is yet to be investigated. Our previous study demonstrated a decrease in ERK‐MAPK and cyclin D1 and an increase in MKP‐1 expression in differentiated osteoblasts following PTH/PTHrP induction both in vitro and in vivo . To investigate the effect of MKP‐1 deletion in PTH1R anabolic action, primary calvarial osteoblasts were isolated from neonatal or 10‐week old MKP‐1 knock out (KO) and wild type (WT) mice via sequential collagenase digestion. The cells were differentiated with ascorbic acid (100μg/ml) and β‐glycerophosphate (5mM) and harvested between 7 to 21 days. Von Kossa staining at day 14 showed decreased mineralization in MKP‐1 KO osteoblasts compared to WT. In contrast to WT cells incubation of MKP‐1 KO osteoblasts with 100nM PTHrP had no effects on pERK or cyclin D1 expression. MicroCT analysis of mid‐diaphyses of tibiae and femora from 2 week old MKP‐1 KO mice showed decreased bone mineral density (BMD), bone mineral content (BMC) and tissue mineral content (TMC) compared to WT bone. Taken together, these results show that MKP‐1 may be important for PTH/PTHrP anabolic action in osteoblasts and play a role in the maintenance of bone mass. (Supported by NIH R03 DE018245‐01 and R01DK53904)