Able Lawrence
179,840 followers -
Physician, Rheumatologist and Immunologist, Closet Geek, Mad about Birds, Photography,technology, statistics, physics, and food. Wanna be philosopher.
Physician, Rheumatologist and Immunologist, Closet Geek, Mad about Birds, Photography,technology, statistics, physics, and food. Wanna be philosopher.
179,840 followers
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Beginnings of a new party?
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LRP1 shedding: Key Pathway in Osteoarthritis uncovered
Therapies for preventing progression of osteoarthritis, the commonest disease that damages the joints have been elusive until now. We already knew that the most important enzymes that degrade the cartilage matrix were ADAMTS5, an aggrecanase and MMT13, a collagenase that degrades type II collagen found in cartilage, but how they were regulated remained a mystery.
While these enzymes are secreted by chondrocytes, they are rapidly taken up back into the cells by LRP1 (Lipoprotein LDL receptor like protein 1) and degraded, LRP1 itself is cleaved sheddases. Increased cleavage of LRP1 in OA or after exposure to inflammatory cytokines further act as decoy receptors increasing the lifetime of these matrix degrading enzymes and increase their aggrecanase degrading activity. The study identified ADAMTS17 and MMP14 as key sheddases and their inhibition restored LRP1 function and protected cartilage matrix from degradation. This opens up a potential new pathway as treatment target in osteoarthritis.
http://onlinelibrary.wiley.com/doi/10.1002/art.40080/full
Therapies for preventing progression of osteoarthritis, the commonest disease that damages the joints have been elusive until now. We already knew that the most important enzymes that degrade the cartilage matrix were ADAMTS5, an aggrecanase and MMT13, a collagenase that degrades type II collagen found in cartilage, but how they were regulated remained a mystery.
While these enzymes are secreted by chondrocytes, they are rapidly taken up back into the cells by LRP1 (Lipoprotein LDL receptor like protein 1) and degraded, LRP1 itself is cleaved sheddases. Increased cleavage of LRP1 in OA or after exposure to inflammatory cytokines further act as decoy receptors increasing the lifetime of these matrix degrading enzymes and increase their aggrecanase degrading activity. The study identified ADAMTS17 and MMP14 as key sheddases and their inhibition restored LRP1 function and protected cartilage matrix from degradation. This opens up a potential new pathway as treatment target in osteoarthritis.
http://onlinelibrary.wiley.com/doi/10.1002/art.40080/full
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