Blood-based biomarkers for detecting mild osteoarthritis in the human knee

Osteoarthritis Cartilage. 2005 Oct;13(10):861-71. doi: 10.1016/j.joca.2005.06.002.


Objective: This study was designed to test the utility of a blood-based approach to identify mild osteoarthritis (OA) of the knee.

Methods: Blood samples were drawn from 161 subjects, including 85 subjects with arthroscopically diagnosed mild OA of the knee and 76 controls. Following RNA isolation, an in-house custom cDNA microarray was used to screen for differentially expressed genes. A subset of selected genes was then tested using real-time RT-PCR. Logistic regression analysis was used to evaluate linear combinations of the biomarkers and receiver operating characteristic curve analysis was used to assess the discriminatory power of the combinations.

Results: Genes differentially expressed (3543 genes) between mild knee OA and control samples were identified through microarray analysis. Subsequent real-time RT-PCR verification identified six genes significantly down-regulated in mild OA: heat shock 90kDa protein 1, alpha; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein; interleukin 13 receptor, alpha 1; laminin, gamma 1; platelet factor 4 (also known as chemokine (C-X-C motif) ligand 4) and tumor necrosis factor, alpha-induced protein 6. Logistic regression analysis identified linear combinations of nine genes--the above six genes, early growth response 1; alpha glucosidase II alpha subunit; and v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian)--as discriminatory between subjects with mild OA and controls, with a sensitivity of 86% and specificity of 83% in a training set of 78 samples. The optimal biomarker combinations were then evaluated using a blind test set (67 subjects) which showed 72% sensitivity and 66% specificity.

Conclusions: Linear combinations of blood RNA biomarkers offer a substantial improvement over currently available diagnostic tools for mild OA. Blood-derived RNA biomarkers may be of significant clinical value for the diagnosis of early, asymptomatic OA of the knee.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Biomarkers / blood*
  • Body Mass Index
  • Female
  • Gene Expression
  • Gene Expression Profiling / methods
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis / methods
  • Osteoarthritis, Knee / diagnosis*
  • Osteoarthritis, Knee / genetics
  • RNA, Messenger / blood
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sensitivity and Specificity
  • Severity of Illness Index


  • Biomarkers
  • RNA, Messenger