To test the idea that SnCs might play a causative role in OA, we used the p16-3MR transgenic mouse, which harbors a p16<sup>INK4a</sup> (Cdkn2a) promoter driving the expression of a fusion protein containing synthetic Renilla luciferase and monomeric red fluorescent protein domains, as well as a truncated form of herpes simplex virus 1 thymidine kinase (HSV-TK).
During OA, chondrocytes (the sole cell type present within articular cartilage) exhibit increased levels of various senescence markers, such as senescence-associated beta-galactosidase (SAβGal) activity, telomere attrition, and accumulation of p16ink4a.
The p19 subunit was abundantly expressed in RA but not in OA synovial tissues. p19 was most prominently expressed by RASF in the synovial lining layer and at the site of invasion, but no heterodimeric IL23 was detected at these sites.
Treated with p16(INK4a)-specific siRNAs, OA chondrocytes displayed a significant decrease in p16(INK4a) expression with an increase of phosphorylated pRb, but no alteration of p14(ARF) and p53 expression, followed by decreases of senescent features and increases in the expression of some chondrocyte-specific genes and overall repair capacity.