The biochemical properties of articular cartilage rely on the biochemical composition and integrity of its extracellular matrix. This matrix consists mainly of a collagen network and the proteoglycan-rich ground substance. In osteoarthritis, ongoing cartilage matrix destruction takes place, leading to a progressive loss in joint function. Beside the degradation of molecular matrix components, destabilization of supramolecular structures such as the collagen network and changes in the expression profile of matrix molecules also take place. These processes, as well as the pattern of cellular reaction, explain the pathology of osteoarthritic cartilage degeneration. The loss of histochemical proteoglycan staining reflects the damage at the molecular level, whereas the supramolecular matrix destruction leads to fissuring and finally to the loss of the cartilage. Chondrocytes react by increasing matrix synthesis, proliferating, and changing their cellular phenotype. Gene expression mapping in situ and gene expression profiling allows characterization of the osteoarthritic cellular phenotype, a key determinant for understanding and manipulating the osteoarthritic disease process.
Objective
Chondrocytes are crucial for adequate matrix balance and function. Cell proliferation and, recently, extensive apoptotic cell death have been reported in osteoarthritic (OA) cartilage. Apoptotic cell death would be an obvious central factor in the initiation and progression of OA, since there is no potential for replacing articular chondrocytes in the adult. Therefore, we studied the occurrence of apoptotic cell disintegration and cell proliferation in OA and normal articular cartilage obtained from the knees of adult donors of all ages.
Methods
Following immunostaining for cellular proteins as well as staining for nuclear DNA, we performed triple‐channel confocal laser scanning microscopy on thick cartilage slices to evaluate lacunar emptying and cell viability. Cell proliferation and apoptotic cell death were evaluated morphologically, by immunodetection of the proliferation‐associated Ki‐67 antigen, and by the TUNEL reaction.
Results
With the exception of the calcified layer, we were not able to detect any major (apoptotic or nonapoptotic) cell disintegration in normal young or aged articular knee cartilage. Single apoptotic cells were detected in OA articular knee cartilage. A significant increase in lacunar emptying was observed in late‐stage specimens with higher Mankin scores compared with age‐matched normal control cartilage specimens, but not in low‐grade lesions. A significant (but lesser) increase in empty lacunae was also observed with age in normal cartilage. Cell proliferation was rarely detected in OA cartilage samples and was not detected at all in normal cartilage samples.
Conclusion
Our results confirm the findings of previous studies showing that cell proliferation occurs in OA cartilage. They also show that, contrary to previous suggestions, apoptotic cell death is not a widespread phenomenon in aging or OA cartilage.
Obesity and excessive lipolysis are implicated in preeclampsia (PE). Intrauterine growth restriction is associated with low maternal body mass index and decreased lipolysis. Our aim was to assess how maternal and offspring fatty acid metabolism is altered in mothers in the third trimester of pregnancy with PE (n=62) or intrauterine growth restriction (n=23) compared with healthy pregnancies (n=164). Markers of lipid metabolism and erythrocyte fatty acid concentrations were measured. Maternal adipose tissue fatty acid composition and mRNA expression of adipose tissue fatty acid-metabolizing enzymes and placental fatty acid transporters were compared. Mothers with PE had higher plasma triglyceride (21%, P<0.001) and nonesterified fatty acid (50%, P<0.001) concentrations than controls. Concentrations of major n-6 and n-3 long-chain polyunsaturated fatty acids in erythrocytes were 23% to 60% lower (all P<0.005) in PE and intrauterine growth restriction mothers and offspring compared with controls. Subcutaneous adipose tissue Δ-5 and Δ-6 desaturase and very long-chain fatty acid elongase mRNA expression was lower in PE than controls (respectively, mean [SD] control 3.38 [2.96] versus PE 1.83 [1.91], P=0.030; 3.33 [2.25] versus 1.03 [0.96], P<0.001; 0.40 [0.81] versus 0.00 [0.00], P=0.038 expression relative to control gene [square root]). Low maternal and fetal long-chain polyunsaturated fatty acid concentrations in PE may be the result of decreased maternal synthesis.
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