Thursday, February 14, 2008

The increase in p-Akt in LSJL

It has been found LSJL increases Akt phosphorylation.  Now where does that increase occur?  In the stem, cells, bone or cartilage.  Ideally, we'd want it to be to increased in the stem cells which would be indicative of ectopic chondrossification.

Akt phosphorylation in human chondrocytes is regulated by p53R2 in response to mechanical stress.

"The p53 tumor-suppressor protein p53R2 is activated in response to various stressors that act on cell signaling. When DNA is damaged, phosphorylation of p53 at its Ser 15 residue induces p53R2 production. The role of p53R2 in chondrocytes remains poorly understood. In this study, we evaluated in chondrocytes, p53R2 expression and its regulation in response to mechanical stress. Furthermore, we investigated the function of p53R2 in relation to mechanotransduction.
Osteoarthritis (OA) cartilage obtained from total knee replacements and normal cartilage obtained from femoral neck fractures was used to measure p53R2 expression. The OA chondrocytes were subjected to a high magnitude of cyclical tensile strain by using an FX-2000 Flexercell system. Next, sulfated glycosaminoglycan (sGAG) production was quantified in these cells. Protein expression of p53R2, and phosphorylation of Akt, p38MAPK, ERK1/2, and JNK was also detected. Akt phosphorylation was detected after transfecting the cells with p53R2-specific small interfering RNA (siRNA).
Expression of p53R2 was significantly increased in OA chondrocytes and in chondrocytes after applying 5% tensile strain to the cells. However, Akt phosphorylation was down-regulated in OA chondrocytes after the strain, and was up-regulated after transfection of p53R2. sGAG protein as well as collagen type II and aggrecan mRNA{both up in LSJL} was increased following transfection of p53R2-specific siRNA after 5% tensile strain.
p53R2 could regulate matrix synthesis via Akt phosphorylation during chondrocyte mechanotransduction."

"The ribonucleotide reductase (RR) small subunit 2 homolog p53R2 is directly regulated by p53 during the supply of nucleotides for the repair of damaged DNA "

"p53R2 interacts with MEK2, the extracellular signal-regulated kinase (ERK) kinase 2-mitogen-activated protein kinase (MAPK) 2, and the molecule immediately upstream of ERK in the Ras–Raf–MAPK signaling cascade. p53R2 negatively modulates serum-induced MEK–ERK activity"

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