Abstract
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.
Highlights
Osteoarthritis (OA) is one of the most common chronic diseases in the United States, and given the aging and obesity of the population, its prevalence is increasing
We examined the role of inflammation in OA by performing knee destabilization surgery on wild type and Receptor for Advanced Glycation End-products (RAGE) knock-out (KO) mice according to established procedures (Xu et al, 2010)
We report that OA was abrogated in RAGE KO mouse knee joints compared to destabilized joints from wild type mice
Summary
Osteoarthritis (OA) is one of the most common chronic diseases in the United States, and given the aging and obesity of the population, its prevalence is increasing. OA is characterized by joint pain, joint effusion, loss of mobility, and deformity that can progress to functional joint failure. OA is associated with several different inherited chondrodysplasia syndromes such as Stickler syndrome, caused by mutations in collagens or other cartilage specific genes. In most adults OA is associated with risk factors such as aging, obesity, repetitive stress, joint misalignment, acute injury, or genetic predisposition. Whether OA is triggered by mechanical stress or by a genetic abnormality, the end result is the same—a painful and progressive degeneration of the articular surface with thinning, fissuring, and loss of the functional, protective articular surface of the joint
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