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Wednesday, June 20, 2018 3:24:25 PM
Prostaglandin E2 Exerts Catabolic Effects in Osteoarthritis Cartilage: Evidence for Signaling via the EP4 Receptor
https://tinyurl.com/ycsu9yfk
Yeah, I know real fun reading but PETX's drug for dog's osteoarthritis has been around for a very long time and even Wikipedia has a puff piece on it.
Elevated levels of PGE(2) have been reported in synovial fluid and cartilage from patients with osteoarthritis (OA). However, the functions of PGE(2) in cartilage metabolism have not previously been studied in detail. To do so, we cultured cartilage explants, obtained from patients undergoing knee replacement surgery for advanced OA...
Quantitative PCR screening of nondiseased and end-stage human knee OA articular cartilage specimens revealed that the PGE(2) receptor EP4 was up-regulated in OA cartilage. Moreover, blocking the EP4 receptor (EP4 antagonist, AH23848) mimicked celecoxib by inhibiting MMP-13, ADAMST-5 expression, and proteoglycan degradation. These results suggest that PGE(2) inhibits proteoglycan synthesis and stimulates matrix degradation in OA chondrocytes via the EP4 receptor. Targeting EP4, rather than cyclooxygenase 2, could represent a future strategy for OA disease modification.
So why did only PETX get around to making daily doses of an EP4 antagonist that convert tired old bones and destroyed cartilage healthy again [kind of - our Border Collie still has obvious evidence of arthritis but she is not inhibited or pained at all despite the enormous energy of the breed]?
The only answer I have found is that the receptor is very complex and then those knee and hip replacements make a lot of money for surgeons.
I suspect the osteosarcoma drug will make more of a splash whenever the Ag delinquents get around to approving it but EP4 receptor antagonist may be the greater moneymaker.
Just dreaming. My wife is really crippled with osteo and very resistant to a knee replacement.
Best, Terry
https://tinyurl.com/ycsu9yfk
Yeah, I know real fun reading but PETX's drug for dog's osteoarthritis has been around for a very long time and even Wikipedia has a puff piece on it.
Elevated levels of PGE(2) have been reported in synovial fluid and cartilage from patients with osteoarthritis (OA). However, the functions of PGE(2) in cartilage metabolism have not previously been studied in detail. To do so, we cultured cartilage explants, obtained from patients undergoing knee replacement surgery for advanced OA...
Quantitative PCR screening of nondiseased and end-stage human knee OA articular cartilage specimens revealed that the PGE(2) receptor EP4 was up-regulated in OA cartilage. Moreover, blocking the EP4 receptor (EP4 antagonist, AH23848) mimicked celecoxib by inhibiting MMP-13, ADAMST-5 expression, and proteoglycan degradation. These results suggest that PGE(2) inhibits proteoglycan synthesis and stimulates matrix degradation in OA chondrocytes via the EP4 receptor. Targeting EP4, rather than cyclooxygenase 2, could represent a future strategy for OA disease modification.
So why did only PETX get around to making daily doses of an EP4 antagonist that convert tired old bones and destroyed cartilage healthy again [kind of - our Border Collie still has obvious evidence of arthritis but she is not inhibited or pained at all despite the enormous energy of the breed]?
The only answer I have found is that the receptor is very complex and then those knee and hip replacements make a lot of money for surgeons.
I suspect the osteosarcoma drug will make more of a splash whenever the Ag delinquents get around to approving it but EP4 receptor antagonist may be the greater moneymaker.
Just dreaming. My wife is really crippled with osteo and very resistant to a knee replacement.
Best, Terry
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