The present study shows that L-glutamine can regulate the expression of the long non-coding RNA NKILA by increasing p-SMAD2/3 to prevent the over-activation of NF-κB, thus protecting chondrocytes in vitro and alleviating the production of inflammatory cytokines and osteoarthritis symptoms in a rat model in vivo. The gene discussed is NFKB1; the disease is osteoarthritis.