The fetal and adult injury response in vivo. (A) Principal component analysis (PCA) of adult and fetal secretomes derived from injured versus uninjured (control) cartilage samples (three biological and two technical replicates/group). PCA comparison shows clustering of adult injured and adult controls indicating a strong and robust difference in protein expression between adult uninjured control animals and animals 3-days post-injury. The fetal samples, although showing a less pronounced response to injury, cluster far away from the adult samples indicating a significant difference between fetal and adult samples. Adult control = red diamonds outlined; adult injured (day 3 post-injury (D3pi)) = red diamonds filled; fetal controls (D1pi) = green squares outlined; fetal injured (D1pi) = green squares filled; fetal control (D3pi) = blue circles outlined; fetal injured (D3pi) = blue circles filled). (B) Volcano plot showing the adult injury response. Three days post-injury, 57 proteins were significantly up-regulated, whereas 67 proteins were significantly down-regulated. The volcano plots indicate neutrophil (asterisk) and acute phase proteins (circles) in adults post-injury compared to the control samples. (C,D) Fetal injured sheep show little differences post-injury compared to uninjured controls (C = 1-day post-injury, D = 3-days post-injury).