PAPPA and osteoarthritis: PAPPA was first identified as a plasma protein from the placenta but was later shown to be involved in several biological processes including regulation of insulin-like growth factor (IGF) bioavailability in many tissues.65 In a gene expression study conducted in primary cartilage samples from patients undergoing joint replacement in hip and knee joints, it was shown that PAPPA was upregulated in osteoarthritis affected cartilage, specifically in hip osteoarthritis.