Apoptosis Associated with Osteoarthritis is Attenuated in Mice Lacking the Receptor for Advanced Glycation End Products (RAGE)

Abstract

ObjectiveIt has been previously shown that chondrocyte apoptosis is associated with the progression of osteoarthritis. The objective of this project was to examine the effects of S100, RAGE, Tgf‐β1, HtrA1 and NF κβ on apoptosis in the progression of osteoarthritis (OA).MethodsSamples of wild type (WT) and RAGE knockout (KO) were assayed for HtrA1, S100, RAGE, TGF‐β1, NF‐kB, TUNEL and evaluated for cartilage degradation four weeks after a knee destabilization procedure.ResultsWe observed positive staining for all biomarkers except TGF‐β1examined in both WT and RAGE KO mice with high Mankin score OA. All biomarkers assayed were present, except HtrA1, in samples with low Mankin score OA. We also observed varying degrees of TUNEL assay staining in both WT and RAGE KO mice. Remarkably, despite similar IHC staining profiles, RAGE KO mice exhibited significantly less cartilage degradation and chondrocyte apoptosis, assayed by TUNEL, compared to WT mice.ConclusionWe conclude that RAGE mediated upregulation of TGF β1 leads to an upregulation of HtrA1 and apoptosis associated with osteoarthritis. This suggests that an inhibition of inflammatory processes involving RAGE may attenuate chondrocyte apoptosis, and slow the progression of OA.