Abstract
BackgroundWhile epidemiological studies have reported a potential role for hypercholesterolemia (HCE) in osteoarthritis (OA), the association between HCE and OA has yet to be clarified. Adipose tissue is a primary locus for cholesterol metabolism and the presence of HCE reportedly causes adipose dysfunction. The knee joint contains adipose tissue in the form of the infrapatellar fat pad (IPFP), which has been shown to contribute to the pathophysiology of OA in the knee via the secretion of inflammatory mediators. However, the effect of HCE on the expression of inflammatory mediators in the IPFP has not been elucidated.MethodsIPFP and synovial tissues (ST) were extracted from 145 subjects with OA, diagnosed by radiography, during total knee arthroplasty. OA patients were divided into three groups according to their total cholesterol levels (Desirable, Borderline high and High) based on the National Cholesterol Education Program Adult Treatment Panel III (NCEPATP III). We examined the expression of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES1), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 using real-time polymerase chain reaction and compared results among the Desirable, Borderline high and High groups.ResultsThe mRNA expression levels of TNF-α, IL-1β, and IL-6 in ST and the IPFP were not significantly different among the three groups. COX-2 mRNA expression in ST and IPFP was likewise not different among the three groups. While the mRNA expression level of mPGES1 in ST was also not significantly different, that of mPGES1 in the IPFP was significantly lower in the High group than in the Desirable and Borderline high groups.ConclusionmRNA levels of mPGES-1 are reduced in the IPFP of knee OA patients with HCE. Additional studies are need to clarify the effect of mPGES-1 down-regulation in OA pathology.
Highlights
While epidemiological studies have reported a potential role for hypercholesterolemia (HCE) in osteoarthritis (OA), the association between HCE and OA has yet to be clarified
Several studies have reported that microsomal prostaglandin E2 synthase-1 (mPGES-1) expression and Prostaglandin E2 (PGE2) production are lower in human adipocytes derived from obese patients and adipose tissue harvested from high fat diet (HFD) mice than those from their non-obese and control counterparts, respectively [16]
While the mRNA expression level of microsomal prostaglandin E synthase-1 (mPGES1) in synovial tissues (ST) was not significantly different (Fig. 2b), that of mPGES1 in the infrapatellar fat pad (IPFP) was significantly lower in the High group than the Desirable and Borderline high groups (Fig. 2d)
Summary
While epidemiological studies have reported a potential role for hypercholesterolemia (HCE) in osteoarthritis (OA), the association between HCE and OA has yet to be clarified. The knee joint contains adipose tissue in the form of the infrapatellar fat pad (IPFP), which has been shown to contribute to the pathophysiology of OA in the knee via the secretion of inflammatory mediators. Numerous reports have suggested that osteoarthritis (OA), rather than being a mechanical stress-related joint disorder, is a metabolic syndrome wherein various risk factors function together to cause disease initiation and/or development. While hypercholesterolemia (HCE) is an established risk factor for cardiovascular disorders, epidemiological studies have reported a Adipose tissue is a primary locus for cholesterol metabolism, and the presence of HCE reportedly causes adipose dysfunction. Several studies have reported that mPGES-1 expression and PGE2 production are lower in human adipocytes derived from obese patients and adipose tissue harvested from high fat diet (HFD) mice than those from their non-obese and control counterparts, respectively [16]. Investigation of the arachidonic acid cascade in the IPFP of OA patients with HCE may unveil a possible mechanism for HCE in the initiation and/or development of OA
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