Detection of pain-related molecules in the subchondral bone of osteoarthritic knees

Clin Rheumatol. 2009 Dec;28(12):1395-402. doi: 10.1007/s10067-009-1258-0.


Knee pain is predominant among osteoarthritis (OA) patients, but the mechanism is poorly understood. We investigated subchondral bone as a source of OA knee pain using immunohistochemistry. Fifteen medial-type OA knees with minimum involvement of the lateral compartment determined by X-ray as well as magnetic resonance imaging that received total knee arthroplasty (TKA) were involved. Each pair of the medial femoral condyle (MFC) and lateral femoral condyle (LFC) was compared obtained at the time of TKA. Osteocartilaginous MFC and LFC specimens were histologically examined and stained with antibodies against cyclooxygenase 1 (Cox-1), cyclooxygenase 2 (Cox-2), substance P, tumor necrosis factor-alpha (TNF-alpha), and neuron-specific class III beta-tubulin (TUJ1), a pan-neuronal marker. Formation of cystic lesions was more frequently seen in the MFC. The lesions were composed of vascular endothelial cells, osteoclasts, and mononuclear cells and were present in similar proportions between the MFC and the LFC. Four out of 15 MFC specimens were positive for Cox-1, 15 for Cox-2, and 13 for TNF-alpha. No LFC specimens were positive for any antibodies. Substance P-positive and TUJ1-positive fibers were found in the subchondral area of the MFC, but not in the LFC. Pathological changes in the subchondral bone can be a source of knee pain, which was detectable by the positive immunoreactivity of substance P, Cox-2, TNF-alpha, and TUJ1, in the subchondral bone of affected compartments. The relatively immediate reduction in pain obtained by TKA might account for the involvement of the subchondral bone in knee pain because most of the affected subchondral plate is excised in TKA (debridement effect of TKA).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arthroplasty, Replacement, Knee
  • Biomarkers / metabolism
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology
  • Cartilage, Articular / surgery
  • Cyclooxygenase 2 / metabolism
  • Female
  • Femur / metabolism
  • Femur / pathology
  • Femur / surgery
  • Humans
  • Immunohistochemistry
  • Knee Joint / metabolism*
  • Knee Joint / pathology
  • Knee Joint / surgery
  • Magnetic Resonance Imaging
  • Male
  • Menisci, Tibial / metabolism*
  • Menisci, Tibial / pathology
  • Middle Aged
  • Osteoarthritis, Knee / metabolism*
  • Osteoarthritis, Knee / pathology
  • Osteoarthritis, Knee / surgery
  • Pain / metabolism*
  • Substance P / metabolism
  • Tubulin / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • Biomarkers
  • TUBB3 protein, human
  • Tubulin
  • Tumor Necrosis Factor-alpha
  • Substance P
  • Cyclooxygenase 2
  • PTGS2 protein, human