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PTH Regulation of CEBP‐delta Expression in MAPK Phosphatase‐1 (MKP‐1) Null Osteoblasts from Male and Female Mice
Author(s) -
Datta Nabanita S,
Vengalil Nathan,
Chukkapalli Sahiti
Publication year - 2016
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.30.1_supplement.1113.1
Subject(s) - medicine , endocrinology , osteoblast , bone resorption , parathyroid hormone , biology , osteoclast , receptor , calcium , genetics , in vitro
Age‐related bone loss is associated with a gradual decline in bone homeostasis characterized by increased bone resorption than formation. The mechanisms of osteoblast bone formation are incompletely understood. Parathyroid hormone (PTH) is an important regulator of bone mass and controls osteoblast (the bone forming cells) and osteoclast (the bone resorbing cells) function. MAPKs are negatively regulated by a family of dual‐specificity phosphatases known as the MAPK phosphatases (MKPs). Previous studies from this laboratory have shown that female MKP‐1 knockout (KO) mice display osteopenia, while male KO mice show osteopetrosis. Insulin‐like growth factor‐1 (IGF‐1) plays an important role in promoting osteoblastic differentiation and PTH anabolic action. CCAAT/enhancer‐binding protein delta (CEBP‐delta), a transcription factor, is an upstream regulator of IGF‐1. In order to dissect the molecular mechanism of PTH action on MKP‐1 and sexual dimorphism, this study examined the expressions of CEBP‐delta using primary osteoblasts from wild type (WT) and MKP‐1 KO mice. Calvarial (skull) osteoblasts from 13–16 week old animals were isolated and differentiated for 7‐ days with ascorbic acid. The cells were then treated with vehicle (control) or PTH (100 nM) for 1–2 hour and harvested. Total cellular RNA was isolated and quantitative real‐time PCR was performed. Results indicated sexual dimorphism on CEBP‐delta expression following PTH treatment in both sexes and genotypes. PTH increased 3 to 6‐fold CEBP‐delta expression in KO males but not in WT males. In contrast, 2 to 4‐fold increase in CEBP‐delta expression was noted in WT females compared to 1.5‐fold in KO animals. These findings suggest involvement of CEBP‐delta expression, at least in part, in increased IGF‐1 expression observed in osteoblasts in the absence of MKP‐1 in males. Taken together, our findings provide new insight into the role of MKP‐1 in CEBP‐delta/ IGF‐1 pathway in osteoblast and sexual dimorphism in bone anabolic action. Support or Funding Information Wayne State University Funding for Research and Education (FMRE)