In an in vitro model in which human chondrocytes cells were cultured and exposed to fibronectin fragments (FN-f) in order to mimic osteoarthritis, the expression of PAPPA was shown to be increased after FN-f exposure.69 In PAPPA-null mice, there was marked increase rate of bone formation70 and homozygous knockouts for PAPPA were 40% smaller than wild-type littermates at birth. This evidence concerns the gene FN1 and osteoarthritis.