Loeser et al. provided direct evidence using an FN-RGD→RGE mutant mouse model (Fn1^RGE/–): under non-loading conditions, both wild-type and Fn1^RGE/– cartilage appeared normal; however, upon high mechanical loading (partial meniscectomy plus forced exercise), Fn1^RGE/– mice exhibited significantly accelerated osteoarthritis progression, with MMP-3 and MMP-13 levels rising by 7.8-fold and 6.4-fold, respectively (Almonte-Becerril et al., 2018). Here, FN1 is linked to osteoarthritis.