dinoprost and Dupuytren-Contracture

Dupuytren's disease is associated with contraction of specialized fibroblasts present in the diseased palmar fascia. Pharmacologic agents were evaluated for their ability to promote or inhibit contraction of Dupuytren's fibroblasts in vitro using a collagen lattice contraction assay. In the first part of the study, lysophosphatidic acid (LPA), serotonin, angiotensin II, and prostaglandin F2 alpha were tested for their ability to promote Dupuytren's fibroblast contraction. Lysophosphatidic acid was found to significantly promote Dupuytren's fibroblast contraction as compared with controls. This response to LPA is dose dependent, with a half-maximal response of 0.07 microM. Angiotensin II, serotonin, and prostaglandin F2 alpha at 1 mM, induced a significant amount of contraction as compared to controls, but the amount of contraction was at least six times less than that observed for LPA. In the second part of the study, prostaglandins E1 and E2 or the calcium blockers nifedipine and verapamil were tested for their ability to inhibit LPA-promoted contraction. It was found that both types of inhibitors partially block LPA-promoted contraction of Dupuytren's fibroblasts. The effect of the various pharmacologic agents on normal palmar fibroblasts was not evaluated. The focus of this study was to examine the regulation of contraction of Dupuytren's fibroblasts. This study demonstrates that LPA is a potent agonist of Dupuytren's fibroblast contraction and that this contraction can be inhibited by specific pharmacologic agents. These findings provide a rational basis for investigating further the clinical use of the calcium channel blockers nifedipine or verapamil and prostaglandins E1 and E2 to control Dupuytren's disease and possibly other fibrotic conditions.

Topics: Alprostadil; Angiotensin II; Calcium Channel Blockers; Dinoprost; Dinoprostone; Dupuytren Contracture; Fibroblasts; Humans; In Vitro Techniques; Lysophospholipids; Muscle Contraction; Nifedipine; Serotonin; Verapamil

This study investigated if the vasoactive prostaglandins, PGE2, and PGF2 alpha, were identifiable in association with nodular myofibroblasts of patients with Dupuytren's disease. Immunocytochemic studies, using antibodies specific for these prostaglandins, have confirmed their association with myofibroblasts. Radioimmunoassay was used to quantitate the prostaglandins. Our results indicate a significant increase of both prostaglandins, especially PGF2 alpha, in Dupuytren's palmar fascia when compared with control fascia. These endogenous prostaglandins may influence the contractile behavior of myofibroblasts in Dupuytren's disease to contribute to the pathobiology of this disorder.

Topics: Dinoprost; Dinoprostone; Dupuytren Contracture; Female; Fibroblasts; Humans; Male; Middle Aged; Muscle Contraction; Muscle, Smooth

The in vitro response of myofibroblasts to prostaglandins F2alpha (a vasoconstrictor) and E2 (a vasodilator) were evaluated in specimens obtained from the Dupuytren's nodules of 12 patients. Fibroblasts from four control samples of palmar fascia were similarly tested. This study demonstrated the ability of prostaglandin F2alpha to induce significant contraction of myofibroblasts. Prostaglandin E2 was noted to cause significant relaxation of myofibroblasts. The contractile/relaxation responses of control fibroblasts to these prostaglandins were minimal.

Topics: Cells, Cultured; Dinoprost; Dinoprostone; Dupuytren Contracture; Fibroblasts; Humans; Muscle Contraction; Muscle Relaxation; Muscles; Prostaglandins E; Prostaglandins F; Silicones