For example, WISP-3 overexpression in normal cartilage (C-28/I2) cells dramatically reduces the expression of ADAMTS-4 and ADAMTS-5, and markedly elevates matrix metalloproteinase-1 (MMP-1) and MMP-10 expression, leading to the degradation of cartilage and the development of osteoarthritis [44]. Here, ADAMTS4 is linked to osteoarthritis.