Effects of misoprostol and prostaglandin E2 on proteoglycan biosynthesis and loss in unloaded and loaded articular cartilage explants.
The effects of misoprostol, a prostaglandin E1 analog, and prostaglandin E2 on proteoglycan biosynthesis and loss were studied in unloaded and mechanically loaded mature bovine articular cartilage explants. The prostaglandins were administered daily at dosages of 0, 10, 100 and 1000 eta g/ml for up to seven days, and proteoglycan biosynthesis determined by measurement of radiolabelled sulfate incorporation. The presence of misoprostol lead to a significant (p < 0.001) dose-dependent inhibition (30%-50%) in proteoglycan biosynthesis which was also dependent on exposure time (p < 0.05). A significant decrease in biosynthesis (34%) was also found for prostaglandin E2, but only at the highest dose (1000 eta g/ml). Proteoglycan catabolism rates were not affected by either substance as assessed by loss of newly synthesized proteoglycan. The application of a continuous cyclic mechanical compressive load (stress of 1.0 MPa at 1 hertz for 24 hours) resulted in a significant inhibition of proteoglycan biosynthesis (up to 50%) as compared to unloaded explants. However, there was no additive effect when mechanical load and misoprostol or prostaglandin E2 were combined. These results suggest that prostaglandins may have a role in the degenerative and repair process in various forms of arthritis where elevated intra-articular levels of prostaglandin E2 are present.
Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York City, NY 10021, USA. torzillip@hss.edu
P A
PA
Torzilli
A M
AM
Tehrany
R
R
Grigiene
E
E
Young
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002358:Cartilage, Articular / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D002417:Cattle; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D066298:In Vitro Techniques; D008297:Male; D016595:Misoprostol / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D010120:Oxytocics / Q000494:pharmacology; D011509:Proteoglycans / Q000096:biosynthesis* / Q000187:drug effects; D013314:Stress, Mechanical; D014867:Water / Q000737:chemistry / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010120:Oxytocics; D011509:Proteoglycans; D014867:Water; D016595:Misoprostol; D015232:Dinoprostone