Mandelin Jami, Liljeström Mikko, Li Tian-Fang, Ainola Mari, Hukkanen Mika, Salo Jari, Santavirta Seppo, Konttinen Yrjö T
Institute of Biomedicine/Anatomy, Biomedicum Helsinki, University of Helsinki, Finland.
J Biomed Mater Res B Appl Biomater. 2005 Jul;74(1):582-8. doi: 10.1002/jbm.b.30244.
Interface tissue between the bone and loosening total hip implant is acidic and highly osteolytic. It is characterized by the formation of cathepsin K positive foreign body giant cells. Similar structures to those found in the normal joint surround the artificial hip joint. Cells in synovial membrane of the artificial hip generate synovial fluid that is called pseudosynovial fluid. Interface tissue fibroblasts are able to produce receptor activator of NF-kappaB ligand (RANKL), which can induce osteoclastogenesis during the loosening process. Western blot analysis indicated that RANKL is present in the pseudosynovial fluid. Pseudosynovial fluid induced cultured peripheral blood mononuclear cells to form multinuclear TRAP positive giant cells. In the presence of osteoprotegerin, the soluble RANKL decoy receptor, the number of TRAP positive multinuclear cells was reduced to half (p < 0.05). The multinuclear cells induced with pseudosynovial fluid contained active cathepsin K protein and were capable of bone matrix resorption in vitro. The cells were shown to express osteoclast phenotype markers, such as mRNA for cathepsin K, TRAP, and calcitonin receptor. It is therefore apparent that pseudosynovial fluid from patients with aseptic loosening of total hip prosthesis contains a potent osteoclastogenic factor RANKL that further suggests a favorable environment for osteoclast formation in the peri-implant tissues. It is thus concluded that suppression of RANKL activity may be beneficial in terms of increasing the lifetime of total hip prostheses.
骨与松动的全髋关节植入物之间的界面组织呈酸性且具有高度溶骨性。其特征是组织蛋白酶K阳性异物巨细胞的形成。人工髋关节周围存在与正常关节中发现的结构相似的结构。人工髋关节滑膜中的细胞产生称为假滑膜液的滑液。界面组织成纤维细胞能够产生核因子κB受体活化因子配体(RANKL),在松动过程中可诱导破骨细胞生成。蛋白质印迹分析表明RANKL存在于假滑膜液中。假滑膜液诱导培养的外周血单核细胞形成多核抗酒石酸酸性磷酸酶(TRAP)阳性巨细胞。在存在骨保护素(可溶性RANKL诱饵受体)的情况下,TRAP阳性多核细胞的数量减少至一半(p<0.05)。用假滑膜液诱导的多核细胞含有活性组织蛋白酶K蛋白,并且能够在体外进行骨基质吸收。这些细胞显示出表达破骨细胞表型标志物,如组织蛋白酶K、TRAP和降钙素受体的mRNA。因此,显然来自全髋关节假体无菌性松动患者的假滑膜液含有一种有效的破骨细胞生成因子RANKL,这进一步表明植入物周围组织中存在有利于破骨细胞形成的环境。因此得出结论,抑制RANKL活性可能有利于延长全髋关节假体的使用寿命。