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Disparate regulation of IGF‐1 in primary osteoblasts isolated from MAPK phosphatase‐1 knockout mice involves AKT/ β‐catenin pathway (802.18)
Author(s) -
Datta Nabanita,
Datta Tanuka,
Mahalingam Chandrika,
Chukkapalli Sahiti
Publication year - 2014
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.28.1_supplement.802.18
Subject(s) - protein kinase b , osteoblast , wnt signaling pathway , endocrinology , medicine , mapk/erk pathway , signal transduction , phosphorylation , pi3k/akt/mtor pathway , p38 mitogen activated protein kinases , chemistry , bone remodeling , microbiology and biotechnology , biology , in vitro , biochemistry
The role of MAPKs in osteogenesis and in Parathyroid hormone (PTH) signaling has been shown in vitro and in vivo previously. However, the role of MAPK phosphatase‐1 (MKP‐1) in bone formation remains unclear. We observed age dependent sexual dimorphism in bone phenotype of MKP‐1 knock out (KO) mice showing osteopenia in females and osteopetrosis in males. We investigate the involvement of MKP‐1 on b‐catenin, a key mediator of the canonical Wnt signaling pathway and an important regulator of bone forming cells, the osteoblasts. Signal transduction through b‐catenin requires inhibition of GSK‐3b which is also inhibited via phosphorylation by AKT upon insulin‐like growth factor‐1 (IGF‐1) signaling. Real‐time PCR analysis of primary calvarial osteoblasts revealed significant down‐regulation of IGF‐1 mRNA expression in osteoblasts isolated from MKP‐1 KO female mice in contrast to KO osteoblasts from males. Inhibition of P‐ERK and P‐p38 with pharmacological inhibitors showed disparate regulation of IGF‐1 expression in WT and KO male and female mice, suggesting MKP‐1/MAPK dependent regulation of IGF‐1. Immunobloting showed diminished AKT phosphorylation and b‐catenin expression in KO osteoblasts in the presence or absence of PTH. Taken together, our findings provide new insight into the role of MKP‐1 in IGF‐1/AKT/b‐catenin pathway in osteoblast which may be of potential biological and pathophysiological importance. Grant Funding Source : Supported by NIH DK087848 and WSU OVPR