Inhibition of collagen aggregation in rat cartilage induced by beta amino propionitrile in vitro

Segments of costal cartilage from rapidly growing rats were incubated in an enriched medium containing L-proline-U-C¹⁴ and varying concentrations of the potent lathyrogenic agent, beta amino propionitrile (BAPN). In parallel experiments, the incorporation of sulfate-S³⁵ was measured under the same conditions, with BAPN concentrations ranging from 1.0 to 1000 μg per milliliter of the incubation medium. With the exception of the highest concentration of BAPN used (910 μg per milliliter of medium), accumulation of collagen, which was insoluble in 0.45M sodium chloride, was inhibited without concomitant inhibition of over-all collagen synthesis, while incorporation of sulfate-S³⁵ remained unchanged. Further experiments demonstrated the partial reversibility of BAPN-induced inhibition. A concentration of BAPN of 910 μg per milliliter inhibited over-all hydroxyproline synthesis, and a similar concentration significantly reduced sulfate uptake. BAPN did not influence the appearance of free hydroxyproline in the medium. It is concluded that BAPN acts directly on cartilage to inhibit collagen aggregation and that this action is not mediated by alterations in chondroitin sulfate synthesis.