Molecular and cellular features of femoral head avascular necrosis: in vivo study

Aim. To study the molecular and cellular features of femoral head avascular necrosis in the rat model.

Materials and Methods. Femoral head avascular necrosis was surgically induced in 8 rats with the 4-week follow-up. Then, the animals have been euthanised, and we performed gross, radiological, and histological examination of avascular and intact contralateral femoral heads. Systemic inflammation was assessed using enzyme-linked immunosorbent assay, and pro-inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor α). The proteomic profile of healthy and necrotic femoral heads was interrogated using sodium dodecyl sulfate polyacrylamide gel electrophoresis and ultra-high performance liquid chromatography-tandem mass spectrometry with ion mobility (TimsToF Pro).

Results. Aseptic necrosis of the femoral head was successfully induced in all rats. Serum levels of pro-inflammatory cytokines (interleukin-1β and interleukin-6) were higher in rats with femoral head avascular necrosis as compared with healthy rats. Among the major proteins revealed at proteomic profiling were those involved in maintaining bone tissue homeostasis, calcium phosphate metabolism, angiogenesis, hematopoiesis, cell-cell interactions, chaperones, cartilage matrix proteins, collagen synthesis, and lipid metabolism. In bones with avascular necrosis, we have also found proteins regulating the inflammatory response and oxidative stress. Sodium dodecyl sulfate polyacrylamide gel electrophoresis indicate that the development of avascular osteonecrosis was accompanied by an overexpression of oxidative stress proteins, anaerobic glycolysis, and non-specific inflammatory response along with the downregulation of molecules responsible for angiogenesis, chondrogenesis, calcium phosphate metabolism, collagen synthesis, and cartilage matrix.

Conclusion. Femoral head avascular necrosis is accompanied by non-specific inflammation, oxidative stress, and lipid peroxidation all presumably developed because of hypoxia and together contributing to bone destruction.

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