In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.

Q: Context: We previously reported that human OA subchondral bone osteoblasts could be discriminated into two subpopulations identified by their levels of endogenous production (low [L] or high [H]) of PGE(2). Here, we investigated the OPG and RANKL expression levels, the histologic analysis of the subchondral bone as well as the osteoclast differentiation effect of osteoblasts on normal and both OA subpopulations (L and H), and further examined on the L OA osteoblasts the modulation of bone remodelling factors on the OPG and RANKL levels, as well as on the resorption activity.', 'Gene expression was determined using real-time PCR, PGE2 and OPG levels by specific ELISA, and membranous RANKL by flow cytometry. Histological observation of the subchondral bone was performed on human knee specimens. Osteoclast differentiation and formation was assayed by using the pre-osteoclastic cell line RAW 264.7. OPG and RANKL modulation on L OA osteoblasts was monitored following treatment with osteotropic factors, and the resorption activity was studied by the co-culture of differentiated PBMC/osteoblasts.', 'Human OA subchondral bone osteoblasts expressed less OPG than normal. Compared to normal, RANKL gene expression levels were increased in L OA and decreased in H OA cells. The OPG/RANKL mRNA ratio was significantly diminished in L OA compared to normal or H OA (p<0.02, p<0.03), and markedly increased in H OA compared to normal. Inhibition of endogenous PGE(2) levels by indomethacin markedly decreased the ratio of OPG/RANKL on the H OA. In contrast to H OA osteoblasts, L OA cells induced a significantly higher level of osteoclast differentiation and formation (p<0.05). Histological analysis showed a reduced subchondral bone on the L OA and an increased bone mass on the H OA compared to normal. Treatment of L OA osteoblasts with osteotropic factors revealed that the OPG/RANKL mRNA expression ratio was significantly reduced by vitamin D(3) and significantly increased by TNF-alpha, PTH and PGE(2), while IL-1Beta demonstrated no effect. OPG protein levels showed similar profiles. No true effect was noted on membranous RANKL upon treatment with IL-1Beta, PGE(2) and PTH, but a significant increase was observed with vitamin D3 and TNF-alpha. The resorption activity of the L OA cells was significantly inhibited by all treatments except IL-1Beta, with maximum effect observed with vitamin D(3) and PGE(2).\Question: Is the differential expression of osteoprotegerin ( OPG ) and receptor activator of nuclear factor kappaB ligand ( RANKL ) in human osteoarthritic subchondral bone osteoblasts an indicator of the metabolic state of these disease cells?

A: OPG and RANKL levels, and consequently the OPG/RANKL ratio, differed according to human OA subchondral bone osteoblast classification; it is decreased in L and increased in H OA. These findings, in addition to those showing that L OA osteoblasts have a reduced subchondral bone mass and induce a higher level of osteoclast differentiation, strongly suggest that the metabolic state of the L OA osteoblasts favours bone resorption.
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Q: Context: The effect of the interaction between type 2 diabetes and dyslipidemia on inflammation and lipid peroxidation (LPO) has not been assessed.', 'To investigate whether diabetes coupled with dyslipidemia alters oxidative metabolism leading to increased LPO products and inflammatory status.', '100 patients were divided into four groups based upon diabetic and dyslipidemic status: poorly controlled diabetes with dyslipidemia (DM-PC/D), well-controlled diabetes with dyslipidemia (DM-WC/D), normoglycemic individuals with dyslipidemia (NG/D), and normoglycemic individuals without dyslipidemia (NG/ND). Plasma was evaluated for an LPO product (MDA), antioxidant levels and inflammatory cytokines.', 'Diabetics presented significantly higher levels of LPO (p<0.05) and the DM-PC/D had higher levels of proinflammatory cytokines and MDA in the plasma in comparison with normoglycemics (p<0.05). Interestingly IL1-β, IL-6, and TNF-α in DM-WC/D were not statistically different from those in DM-PC/D. Normoglycemic individuals with dyslipidemia presented significantly increased levels of IL-6 and TNF-α when compared to normoglycemic without dyslipidemia (p<0.05). MDA levels were also positively correlated with the presence of DM complications (r=0.42, p<0.01).\Question: Are diabetes and increased lipid peroxidation associated with systemic inflammation even in well-controlled patients?

A: These findings show that dyslipidemia is associated with an increased inflammatory status, even in well-controlled diabetics and in normoglycemics. Our results suggest that lipid metabolism and peroxidation are important for the development of inflammation, which is elevated in several complications associated with diabetes.
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Q: Context: Ischemia-reperfusion injury (IRI) to the lower extremities causes both local damage and serious dysfunction to remote organs, including lungs and kidneys. However, effective therapies are not available. This study aims to determine if simvastatin reduced the severity of remote damage following IRI.', 'Rats were given simvastatin before hind limb IRI. Lung and kidney tissues were assessed for neutrophil infiltration using myeloperoxidase assays and basement membrane damage by quantitative immunohistochemical measurement of collagen IV. The effect of nitric oxide synthase (NOS) inhibition on remote damage after IRI and simvastatin was assessed using the NOS inhibitor, L-NIO.', 'Simvastatin (2 mg/kg) protected kidneys against IRI-induced neutrophil infiltration. Simvastatin also inhibited the IRI-induced activation of MMP-9 in the lungs. However, paradoxically, simvastatin exacerbated IRI-induced neutrophil infiltration into the lungs. IRI induced collagen IV degradation in the lungs but not in the kidneys. The degree of collagen breakdown in the lungs was significantly ameliorated by 2 mg/kg simvastatin. NOS inhibition markedly protected both the lungs and the kidneys against IRI-induced neutrophil infiltration but did not alter collagen IV degradation. Administration of simvastatin to L-Nio-treated animals enhanced the degree of protection against IRI-induced neutrophil infiltration in the kidneys but not in the lungs.\Question: Does simvastatin plus nitric oxide synthase inhibition modulate remote organ damage following skeletal muscle ischemia-reperfusion injury?

A:
Simvastatin protects against remote IRI-induced damage in the lungs and kidneys, suggesting statins may reduce the severity of IRI during major vascular surgery.
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