Fig. 8From: USP24-dependent stabilization of Runx2 recruits a p300/NCOA3 complex to transactivate ADAMTS genes and promote degeneration of intervertebral disc in chronic inflammation miceSchematic model for the degeneration of IVDs by the transactivation of ADAMTS genes by the NCOA3-p300-pRunx2 complex(A) Schematic model of the transactivation of ADAMTS genes by the NCOA3-p300-pRunx2 complex in the degeneration of IVDs. Chronic inflammation activates p38 kinase, which phosphorylates Runx2 at the Ser28 site. pRunx2S28 then recruits p300 and NCOA3 to assemble a complex that binds to the promoters of ADAMTS1/4/5/6/7/8/9/10/12/13/14/15/16/17/18/20 to transactivate their expression. The induction of these ADAMTS genes promotes ECM degradation and leads to IDD. (B) Schematic model depicting how inhibition of the NCOA3-p300-pRunx2 complex decreases the degeneration of IVDs. Administration of p38/NCOA3/p300 inhibitors in LPS-challenged mice decreases the expression of ADAMTS1/4/5/6/7/8/9/10/12/13/14/15/16/17/18/20, thereby retarding ECM degradation and slowing the IDD processBack to article page