HtrA1, Ddr-2, and Mmp-13 are reliable biomarkers for osteoarthritis (OA), yet the exact mechanism for the upregulation of HtrA-1 is unknown. Some have shown that chondrocyte hypertrophy is associated with early indicators of inflammation including TGF-β and the Receptor for Advanced Glycation End-products (RAGE). To examine the correlation of inflammation with the expression of biomarkers in OA, we performed right knee destabilization surgery on 4-week-old-wild type and RAGE knock-out (KO) mice. We assayed for HtrA-1, TGF-β1, Mmp-13, and Ddr-2 in articular cartilage at 3, 7, 14, and 28 days post-surgery by immunohistochemistry on left and right knee joints. RAGE KO and wild type mice both showed staining for key OA biomarkers. However, RAGE KO mice were significantly protected against OA compared to controls. We observed a difference in the total number of chondrocytes and percentage of chondrocytes staining positive for OA biomarkers between RAGE KO and control mice. The percentage of cells staining for OA biomarkers correlated with severity of cartilage degradation. Our results indicate that the absence of RAGE did protect against the development of advanced OA. We conclude that HtrA-1 plays a role in lowering TGF-β1 expression in the process of making articular cartilage vulnerable to damage associated with OA progression.
Polyethylene (PE) remains the gold standard for the articulating surface in hip and knee arthroplasty. To increase arthroplasty longevity and improve wear resistance, newer versions of PE have been designed with resultantly different wear properties. Highly cross-linked polyethylene (HXLPE) is used in total hip arthroplasty with excellent outcomes; however, its use in total knee arthroplasty (TKA) remains conflicting. This review summarizes biomechanical and wear properties, clinical outcomes, and cost of polyethylene inserts in TKA. Simulation studies have convincingly shown decreased wear and oxidation rates with HXLPE when compared to conventional polyethylene (CPE). Registry results have been conflicting, and short-to midterm clinical studies have not demonstrated a significant difference between HXLPE and CPE. The cost of HXLPE inserts is higher than CPE. Long-term clinical data are lacking and further studies are warranted to evaluate the role of HXLPE in TKA.
HtrA1 and Mmp‐13 are reliable biomarkers of osteoarthritis (OA) and are upregulated at days post knee destabilization surgery (Polur et al., 2010). While expression of RAGE and its ligands are suggested, the exact mechanism for HtrA1 upregulation is not known (Cecil et al., 2005; Loeser et al., 2005). Our objective was to examine biomarkers of OA in the presence (control mice) and absence (RAGE knock‐out) of RAGE. We performed right knee destabilization and sham surgery on 8 week old control and RAGE knock‐out (KO) mice. We assayed for HtrA1, Mmp‐13, RAGE and S‐100 at 3, 7, 14 and 28 days post‐surgery by immunohistochemistry on both knee joints. We did not detect biomarkers of OA including Mmp‐13 in any sham surgery mice. In RAGE KO mice, we observed negligible staining of HtrA1 and faint staining of S‐100 at 28 days post‐surgery but not Mmp‐13. In contrast, we detected the presence of S‐100, HtrA1 and Mmp‐13 at focal points 3 days post‐surgery in control mice. By 28 days post‐surgery HtrA1 and Mmp‐13 expression is uniformly expressed in articular cartilage in control mice. RAGE KO does not entirely prevent HtrA1 upregulation but does protect against Mmp‐13 activation. Since the expression of Mmp‐13 is a terminal event resulting in OA, we conclude that RAGE KO protects against the most vital component of articular cartilage degradation and subsequently, OA.
We have previously shown that knockout (KO) mice lacking the Receptor for Advanced Glycation End Products (RAGE) demonstrate attenuated osteoarthritis (OA) in articular cartilage of the knee. The objective of this research is to discover if knocking out RAGE has a similar protective effect in the condylar cartilage of the Temporomandibular joint (TMJ). Misalignment of the TMJ of Wild‐type (WT) and RAGE KO mice was performed, and severity of OA was assessed along with immunohistochemical staining of several known biomarkers of OA. An inverse relationship is known to exist between the expression of Htra1 and TGF‐B 1 in association with OA. We observed a reciprocal expression of these two proteins in WT but not RAGE KO mice. Condylar cartilage, unlike articular cartilage, has been shown to self‐repair when stress is applied. We hypothesize that the WT mice expressed higher levels of TGF‐B 1 as a result of natural repair processes. In contrast, RAGE KO mice lacked this pattern, suggesting that this receptor may play a role in the natural repair of condylar cartilage of the TMJ.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.