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.
Furthermore, osteoclast bone resorption activity was elevated, as reflected by increased expression of the lysosomal protease cathepsin K. However, the insertion allele of the NOD1 +32656 polymorphism was not associated with either susceptibility to, or clinical parameters of, inflammation or bone destruction in RA patients.
In order to clarify the contribution of cathepsin K to the destruction of arthritic bone, we applied the human tumor necrosis factor (hTNF)-transgenic mouse model, in which severe polyarthritis characterized by strong osteoclast-mediated bone destruction develops spontaneously.
Interface tissue fibroblasts are able to produce RANKL, OPG, and cathepsin K and may contribute indirectly and directly to pathologic periprosthetic collagenolysis and bone destruction.