ACAN and intervertebral disk degenerative disorder: In vivo human IDD or in vitro TNF-α treatment led to decreased expression of SHOX2.161 Treatment with SHOX2 siRNA inhibited the proliferation and apoptosis of NP cells, decreased aggrecan and collagen II expression, and increased MMP3 and ADAMTS-5 production in NP cells.161 These results indicated that SHOX2 has a protective effect in the IVD and is worth further investigation.