Back to Search
Start Over
A novel PPARγ agonist, KR62776, suppresses RANKL-induced osteoclast differentiation and activity by inhibiting MAP kinase pathways
- Source :
-
Biochemical & Biophysical Research Communications . Jan2009, Vol. 378 Issue 3, p645-649. 5p. - Publication Year :
- 2009
-
Abstract
- Abstract: We investigated the effects of a novel peroxisome proliferator-activated receptor γ (PPARγ) agonist, KR62776, on osteoclast differentiation and function, and on the underlying signaling pathways. KR62776 markedly suppressed differentiation into osteoclasts in various osteoclast model systems, including bone marrow mononuclear (BMM) cells and a co-culture of calvarial osteoblasts and BMM cells. KR62776 suppressed the activation of tartrate-resistant acid phosphatase (TRAP) and the expression of genes associated with osteoclast differentiation, such as TRAP, dendritic cell-specific transmembrane protein (DC-STAMP), and osteoclast-associated receptor (OSCAR). Furthermore, KR62776 reduced resorption pit formation in osteoclasts, and down-regulated genes essential for osteoclast activity, such as Src and αvβ3 integrin. An analysis of a signaling pathway showed that KR62776 inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced activation of p38 mitogen-activated protein kinase (p38MAPK), extracellular regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF-κB). Together, these results demonstrate that KR62776 negatively affects osteoclast differentiation and activity by inhibiting the RANKL-induced activation of MAP kinases and NF-κB. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 378
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 35943580
- Full Text :
- https://doi.org/10.1016/j.bbrc.2008.11.115