Are Altered Proteins the Key to Hip Osteonecrosis?

It’s hard to have a comprehensive joint-preserving strategy if you lack the full picture on cartilage destruction in early osteonecrosis of the femoral head. To rectify this, a team of researchers from China undertook a study, “Proteomics analysis of hip articular cartilage identifies differentially expressed proteins associated with osteonecrosis of the femoral head.” This research appears in the July 1, 2021 edition of Osteoarthritis and Cartilage.

“Osteonecrosis of the femoral head is a refractory orthopedic disease causing progressive avascular bone necrosis and substantial loss of the hip joint function,” co-author and medical student Jidong Song of Xi’an Jiaotong University in Shaanxi, China explained to OTW.

“It usually affects young, active adults between the ages of 20 and 50 and progresses to collapse of the femoral head in 80% of untreated patients. It is estimated that there are 8.12 million osteonecrosis of the femoral head cases in China. However, the pathogenesis of articular cartilage degeneration in osteonecrosis of the femoral head patients is often underappreciated and still unclear.”

“To better understand the molecular basis of cartilage degradation in osteonecrosis of the femoral head, based on the isobaric tandem mass tag high throughput proteomics strategy, we compared the proteomic profiles of osteonecrosis of the femoral head cartilage with that of fracture control. This study, a proteomics analysis of hip cartilage, is a continuation of our previous series of osteonecrosis of the femoral head omics studies.”

Pitting 16 hip cartilage samples from patients with osteonecrosis of the femoral head against a control group of 16 patients with femoral neck fracture, the researchers used proteomics, gene ontology analysis, and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway and protein–protein interaction analysis to map the functions of the altered proteins and biological pathways. The team looked at differentially expressed proteins including alpha-2-HS-glycoprotein and cytokine-like protein, which were validated by Western blot and immunohistochemistry.

According to Jidong Song the study compared protein expression profiles of hip articular cartilage in osteonecrosis of the femoral head and fracture controls in a comprehensive and large-scale manner. “We identified a number of differentially expressed proteins and pathways between osteonecrosis of the femoral head and fracture controls that may provide novel clues for pathogenesis studies of cartilage degradation in osteonecrosis of the femoral head. We hope that this study, together with our previous omics studies, will lay some groundwork for the precise treatment of early osteonecrosis of the femoral head.”

“We identified 303 differentially expressed proteins in osteonecrosis of the femoral head cartilage with 72 up-regulated and 231 down-regulated. Collagen turnover, glycosaminoglycan biosynthesis, metabolic pathways, and complement and coagulation cascades were significantly modified in osteonecrosis of the femoral head cartilage.”

“Western blotting and immunohistochemical analysis confirmed the increased expression of alpha-2-HS-glycoprotein and decreased expression of cytokine-like protein 1 in osteonecrosis of the femoral head cartilage.”