Disparate regulation of IGF‐1 in primary osteoblasts isolated from MAPK phosphatase‐1 knockout mice involves AKT/ β‐catenin pathway (802.18)

Autor: Sahiti Chukkapalli, Chandrika D Mahalingam, Tanuka Datta, Nabanita S. Datta
Rok vydání: 2014
Předmět:
Zdroj: The FASEB Journal. 28
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fasebj.28.1_supplement.802.18
Popis: 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 express...
Databáze: OpenAIRE
Externí odkaz: