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Fig. 8 | Biology Direct

Fig. 8

From: USP24-dependent stabilization of Runx2 recruits a p300/NCOA3 complex to transactivate ADAMTS genes and promote degeneration of intervertebral disc in chronic inflammation mice

Fig. 8

Schematic 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 process

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Biology Direct

ISSN: 1745-6150

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