Collagen-affecting drugs impair regeneration of teleost tail fins.

Regenerating tail fins were studied in two species of teleosts, Tilapia rendalli and Cyprinus carpio, treated with indomethacin, aspirin, dexamethasone, penicillamine, and beta-aminoproprionitrile, drugs known to disrupt collagen metabolism in mammals. Collagen was studied under the light microscope by the Picrosirius-polarization method and also under the electron microscope. In general, these drugs disturbed the deposition and organization of collagen fibrils leading to abnormally thin or practically absent lepidotrichia and actinotrichia, and also to disorganized fibrous connective tissue. The resulting disorganization of the collagenous scaffolding of the regenerating dermoskeleton was probably responsible for a secondary effect on blastema distalization and on the general fin ray patterning that were also observed. The foregoing observations suggest that the stromal histoarchitecture of the regenerate plays a vital role in fin regeneration and indicate that these drugs may be useful in studying the extracellular matrix-cell interactions at the cellular and molecular level. In addition, the present findings provide a basis for developing different biological models by using teleost fin regeneration.

Effect of beta-aminoproprionitrile on eggshell formation.

1. Eggshells are bioceramic-biopolymer composites made by a cell-mediated deposition of an extracellular matrix which drives the organisation of the inorganic phase. Ultrastructurally, eggshells are composed of shell membranes, mammillary knobs, palisade, and cuticle. Shell membranes are two nets of type X collagen-containing fibrils. On to these membranes, the mammillary knobs, that is, the crystal nucleation sites, are deposited. Type X collagen is highly cross-linked and insoluble. 2. In order to evaluate the role of type X collagen cross-linking on eggshell formation, hens were injected with different doses of beta-aminoproprionitrile, which specifically interferes with cross-link formation. 3. Changes in egg size and shape were observed. Scanning electron micrographs analysis of these eggs demonstrated marked changes in crystal growth and shell membrane structure and arrangement. A dot-blot analysis, using a monoclonal antibody against chicken type X collagen, shows a dose-dependent increase in shell membrane collagen extractability. 4. It is concluded that the formation of beta-aminoproprionitrile-sensitive cross-links among the type X collagen molecules of the shell membranes play an essential role in normal eggshell formation.

Effects of chronic beta-aminoproprionitrile treatment on rat carotid artery.

The effects of chronic treatment of young rats (initially 8 weeks old) with the collagen cross-linking inhibitor, beta-aminoproprionitrile (BAPN), on arterial wall properties were studied. BAPN was added to the drinking water for 8 weeks to produce intakes of 0, 100, 200 and 400 mg/kg/day. Systolic pressure of treated animals did not increase with age as rapidly as that of untreated controls. Weight gain of treated animals was inhibited at the highest (BAPN) treatment level. Passive stiffness of isolated, cylindrical segments of carotid arteries was decreased in BAPN-treated animals in a dose-dependent manner. BAPN treatment had no significant effect on the total collagen or elastin content (hydroxyproline) of carotid arteries. Values of maximum active force development to 10 microM norepinephrine plus 75 mM K+ were decreased by BAPN treatment in a dose-dependent manner. There was no significant effect of BAPN treatment on total water content or its cellular and extracellular components in the carotid artery. The relative cell volume of carotid arteries was not altered by BAPN treatment, suggesting that the decreased force development was a characteristic of individual cells. These results suggest that BAPN treatment may decrease stiffness by altering secondary characteristics of the connective tissue matrix without affecting connective tissue content. The decreased maximum smooth muscle force development may be responsible for the blood pressure-lowering effects of BAPN.