This 2008 CORR editorial revisits Ponseti's 1957 experiments on aminonitrile-induced skeletal disease. Ponseti fed aminonitriles to growing animals to test whether these compounds cause the skeletal lesions of lathyrism. The commentary situates the work within the historical understanding of lathyrism and connective tissue biology.
Lathyrism is the classic model for understanding collagen crosslinking and its failure. Aminonitriles (notably BAPN) inhibit lysyl oxidase, the enzyme that crosslinks collagen and elastin. When crosslinking fails, connective tissue loses tensile strength wherever it bears load.
That single mechanism explains the paper's scattered findings: growth plates slip, spines deform into scoliosis and kyphosis, and the aorta dissects. For a trainee, the mental model is that a toxin targeting one structural protein pathway can produce disease across bone, cartilage, ligament, and vessel simultaneously.
This experimental lineage is also part of why Ponseti's name is attached to careful mechanistic study of skeletal deformity, foreshadowing the deformity-focused thinking behind his later clubfoot work.
This 2008 CORR editorial revisits Ponseti's 1957 experiments on aminonitrile-induced skeletal disease. Ponseti fed aminonitriles to growing animals to test whether these compounds cause the skeletal lesions of lathyrism. The commentary situates the work within the historical understanding of lathyrism and connective tissue biology.
Lathyrism is the classic model for understanding collagen crosslinking and its failure. Aminonitriles (notably BAPN) inhibit lysyl oxidase, the enzyme that crosslinks collagen and elastin. When crosslinking fails, connective tissue loses tensile strength wherever it bears load.
That single mechanism explains the paper's scattered findings: growth plates slip, spines deform into scoliosis and kyphosis, and the aorta dissects. For a trainee, the mental model is that a toxin targeting one structural protein pathway can produce disease across bone, cartilage, ligament, and vessel simultaneously.
This experimental lineage is also part of why Ponseti's name is attached to careful mechanistic study of skeletal deformity, foreshadowing the deformity-focused thinking behind his later clubfoot work.