Immunohistochemistry results revealed p21<sup>-/-</sup> mice susceptibility to OA changes accompanied by macrophage infiltration and enhanced MMP-3 and MMP-13 expression through IL-1β-induced NF-κB signaling. p21<sup>-/-</sup> mice also showed subchondral bone destruction according to micro-CT analysis, and cathepsin K staining revealed increased numbers of osteoclasts.
This study supports the supposition that H(4)R in synovial tissue may play a role in cartilage and bone destruction by influencing the secretion of MMP-3 in patients with RA.