MMP13 and atrial fibrillation: In particular, PGRN-/-mice significantly exhibits: (i) higher levels of osteoblast gene markers and osteoclast activity; (ii) proteoglycan loss, especially in AF and CEP; (iii) degradation of aggrecan; (iv) increased levels of ADAMTS-5 and MMP-13; (v) dramatic augment of pIκB-α levels; (vi) elevated levels of iNOS, both mRNA and protein; and (vii) greater activation of β-catenin signaling pathway, evidenced by higher levels of mRNA, protein, nuclear translocation and downstream proteins, namely Axin2 and RUNX2 [65].