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

Abstract

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).

Pain Perception in Knees With Circumscribed Cartilage Lesions Is Associated With Intra-articular IGF-1 Expression

“…The relatively immediate reduction in pain obtained by TKA (total knee arthroplasty) might account for the involvement of the subchondral bone in knee pain because most of the affected subchondral plate is excised in TKA. 36 These data are supported by our finding that KLS is correlated with pain strength. The role of bone marrow lesions in the development of pain still remains doubtful, 48 but it has been shown that subchondral bone marrow edema at the time of treatment represents a negative prognostic factor for early outcome after ACI.…”

Angiogenic activity of subchondral bone during the progression of osteoarthritis in a rabbit anterior cruciate ligament transection model

“…Elevated vascularity has been reported at the osteochondral junction of end-stage osteoarthritic knees compared to normal controls 1,2 . In addition, elevated vasculature was observed in subchondral bone in the medial compartment compared to the lateral compartment in medial-type osteoarthritic knees 3 , and elevated vascularization associated with innervation of sensory and sympathetic nerves into cartilage was detected at osteochondral junction in end-stage osteoarthritic knees 4 . All of these results suggest a strong association between severity of OA and vascularity of the osteochondral junction; however, when the actual invasion occur remains to be elucidated.…”

Objective assessments of medial osteoarthritic knee severity by MRI: new computer software to evaluate femoral condyle contours

“…Sclerotic lesions are a mixture of thin and thick subchondral bone as OA becomes more severe. In our previous study, the cystic lesions of sclerotic lesions were positively stained with antibodies against pain-related molecules, including cyclooxygenase-2 (COX-2) and tumour necrosis factor alpha (TNF-α) [23]. Thus, we speculated that the subchondral bone of the affected compartment could be a source of pain, and that the extent of corresponding pathological changes that occurred in subchondral bone could be assessed by newly developed software presented in this paper.…”