Inhibition of LRP1 shedding reverses cartilage degradation in osteoarthritis

Purpose: There is no clear correlation between mRNA levels of ADAMTS5 and progression of osteoarthritis (OA). We have found that ADAMTS5 is constitutively produced in healthy human cartilage, but are rapidly taken up and degraded intracellularly by the chondrocytes via the low-density lipoprotein receptor-related protein 1 (LRP1). Other proteins that are endocytosed by LRP1 include ADAMTS4, MMP13 and TIMP3, indicating that LRP1 is a key...