Basic calcium phosphate crystals activate c-fos expression through a Ras/ERK dependent signaling mechanism. Biochem Biophys Res Commun 2007 Apr 13;355(3):654-60
Date
02/20/2007Pubmed ID
17307136Pubmed Central ID
PMC1855205DOI
10.1016/j.bbrc.2007.01.177Scopus ID
2-s2.0-33847287739 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
Diseases caused by calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystals occur frequently in osteoarthritic joints. Both crystals induce mitogenesis, metalloproteinase synthesis and secretion by fibroblasts and chondrocytes, promoting degradation of articular tissue. We investigated the mechanism by which BCP activates the c-fos proto-oncogene, which has been shown to activate various matrix metalloproteinases (MMPs). We demonstrate that BCP crystals induce c-fos expression primarily through a Ras/ERK-dependent signaling mechanism targeting two highly conserved regulatory binding sites, the serum response element (SRE) and the cAMP response element (CRE). These results establish a calcium crystal induced, calcium/calmodulin independent, signaling pathway in which BCP crystals activate Ras/MAPK, which can directly target an SRF-containing transcription factor complex, to induce fibroblasts to secrete metalloproteinases.
Author List
Major ML, Cheung HS, Misra RPAuthor
Ravindra P. Misra PhD Associate Provost, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCalcium Phosphates
Cells, Cultured
Crystallization
Cyclic AMP
Extracellular Signal-Regulated MAP Kinases
Humans
Mice
Oncogene Protein p21(ras)
Osteoarthritis
Proto-Oncogene Proteins c-fos
Response Elements
Serum Response Element
Signal Transduction
