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

Detection of pain-related molecules in the subchondral bone of osteoarthritic knees
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DOI:
10.1007/s10067-009-1258-0
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发表时间:
2009-12-01
影响因子:
3.4
通讯作者:
Moriya, Hideshige
Moriya, Hideshige
中科院分区:
医学3区
文献类型:
--
作者:
Ogino, Shuhei;Sasho, Takahisa;Moriya, Hideshige

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膝关节疼痛在骨关节炎(OA)患者中占主导地位,但其机制知之甚少。我们使用免疫组织化学方法研究了软骨下骨作为OA膝关节疼痛的来源。15个内侧型OA膝关节,通过X线和磁共振成像确定外侧间室受累最小,接受全膝关节置换术(TKA)。比较TKA时获得的每对股骨内侧髁(MFC)和股骨外侧髁(LFC)。对骨软骨MFC和LFC标本进行组织学检查,并用抗环氧合酶1(考克斯-1)、环氧合酶2(考克斯-2)、P物质、肿瘤坏死因子-α(TNF-α)和神经元特异性III类β-微管蛋白(TUJ 1)(一种泛神经元标记物)的抗体染色。囊性病变的形成更常见于MFC。病变由血管内皮细胞、破骨细胞和单核细胞组成,MFC和LFC之间的比例相似。15份MFC标本中有4份考克斯-1阳性,15份考克斯-2阳性,13份TNF-α阳性。无LFC标本的任何抗体呈阳性。P物质阳性和TUJ 1阳性纤维被发现在MFC的软骨下区,但不是在LFC。软骨下骨的病理变化可能是膝关节疼痛的一个来源,这可以通过受影响的隔室的软骨下骨中的P物质、考克斯-2、TNF-α和TUJ 1的阳性免疫反应性检测到。通过TKA获得的相对即时的疼痛减轻可能是膝关节疼痛涉及软骨下骨的原因,因为大部分受影响的软骨下板在TKA中被切除(TKA的清创效应)。
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).