Mild degenerative changes of hip cartilage in elderly patients: an available sample representative of early osteoarthritis

Abstract

This study investigated the cellular and molecular changes which occur in cartilage from adults with femoral neck fracture (FNF) and osteoarthritis (OA), and explored the similarities in hip cartilage obtained from elderly patients and patients with early OA. Femoral heads were retrieved from 23 female patients undergoing total hip arthroplasty (THA). This group included 7 healthy patients with FNF (hFNF), 8 elderly adults with FNF (eFNF), and 8 elderly patients with hip OA (OA). After high-field MRI T2 mapping, osteochondral plugs were harvested from the weight-bearing area of femoral heads for subsequent macroscopic, histologic, and immunochemical evaluation. Additionally, the contents of cartilage matrix were analyzed, and gene expression was detected. The surface of cartilage from hFNF and eFNF patients appeared smooth, regular, and elastic, whereas it showed irregularities, thinning, and defects in OA patients. Elevated T2 values and decreased accumulation of glycosaminoglycans (GAGs) were detected in cartilage from eFNF patients. Furthermore, type I collagen accumulation was slightly increased and type X collagen concentration was obviously elevated in eFNF patients; however, type II collagen distribution and the contents and anisotropy of collagen fibrils in eFNF patients showed no significant changes. Consistent with histology and immunohistochemical results, aggrecan was downregulated and type X collagen was upregulated, while collagens types I and II showed no significant changes in eFNF patients. The cellular and molecular characteristics of hip cartilage in eFNF patients who showed no symptoms of OA were similar to those in patients with mild OA. Thus, eFNF cartilage can serve as a comparative specimen for use in studies investigating early OA.

Keywords: Femoral neck fracture; articular cartilage degeneration; available sample; elderly patients; osteoarthritis.

Figure 1

Results of high-field MRI T2 mapping, macroscopy, and determination of water contents. A, D, G: Anterior-posterior X-rays of hip joints. Red arrows denote the region of femoral neck fracture (FNF) and white arrows denote hip osteoarthritis. B, E, H: Cartilage T2 mapping demonstrated higher signal intensity in elderly adults with FNF (eFNF) compared to healthy patients with FNF (hFNF), but lower signal intensity than in elderly adults with hip OA (OA). C, F, I: Cartilage-bone plugs (8 mm diameter) punched from the femoral heads of hFNF and eFNF patients were smooth and regular in appearance, while cartilage-bone plugs punched from femoral heads of OA patients appeared irregular, thin, and defective. J: The average T2 value for eFNF cartilage was significantly higher than that for hFNF cartilage (P < 0.001), but lower than that for OA cartilage (P < 0.001). K: Water content in eFNF cartilage was insignificantly higher than that in hFNF cartilage (P = 0.351), but significantly lower than that in OA cartilage (P = 0.012). *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 2

Cell morphology and proteoglycan accumulation. (A, B) Chondrocytes and proteoglycans were regularly distributed in hFNF cartilage, (C, D) whereas slightly hypertrophic chondrocytes were showed in the superficial layer of eFNF cartilage and reduced SO staining were detected in the upper and intermediate zone of cartilage. (E, F) An uneven distribution of chondrocyte clusters and marked loss of SO staining in all layers were shown in OA cartilage. (G) The total DNA contents of hFNF and eFNF were significantly higher than that of OA cartilage, while hFNF and eFNF cartilage showed no significant differences in DNA contents. (H) Amounts of GAG were higher in hFNF cartilage compared to eFNF cartilage, and much higher than amounts in OA cartilage. Magnification ×40. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 3

Collagen distribution. A-C: Type II collagen was uniformly distributed throughout the cartilage zones, whereas types I and type X collagen were not detected in the hFNF cartilage. D: Distribution of type II collagen showed no obvious changes in all layers of eFNF cartilage. E, F: However, a slightly increased accumulation of type I collagen and an obviously enhanced concentration of type X collagen were found in the superficial and deep regions of eFNF cartilage. G: Furthermore, type II collagen concentrations were reduced throughout the upper region of cartilage, H, I: whereas deposition of collagens type I and X were increased mainly around chondrocyte clusters in OA cartilage. J: However, there were no significant differences in the total collagen contents of the different groups. Magnification ×40.

Figure 4

Anisotropy of collagen fibrils. A, B: PLM revealed normal organization of collagen fibrils in cartilage from both hFNF and eFNF patients. C: However, disruption of birefringence and disordered collagen fibers were shown in cartilage from OA patients. Magnification ×40.

Figure 5

Gene expression. A: ACAN levels in hFNF cartilage were somewhat higher than those in eFNF cartilage (P = 0.023), and much higher than those in OA cartilage (P < 0.001). B: Levels of COL2 in eFNF cartilage was higher than that in OA cartilage (P = 0.043), whereas no significant difference was detected between eFNF and hFNF cartilage (P = 0.684). C: Levels of COL1 in eFNF cartilage was significantly lower than those in OA cartilage (P < 0.001), there was no obvious difference found in eFNF and hFNF cartilage (P = 0.141). D: Levels of COL10 in hFNF cartilage were lower than those in eFNF cartilage (P = 0.003) and OA cartilage (P = 0.001). *P < 0.05, **P < 0.01, ***P < 0.001.