Gallo J, Zdařilová A, Rajnochová Svobodová A, Ulrichová J, Radová L, Smižanský M
Ortopedická klinika LF UP a FN Olomouc.
Acta Chir Orthop Traumatol Cech. 2010 Oct;77(5):416-24.
A failure of total hip or knee artroplasty is associated with an increased production of joint fluid. This contains wear particles and host cells and proteins, and is assumed to be involved in the pathogenesis of aseptic loosening and periprosthetic osteolysis. This study investigated the effect of synovial fluid from patients with aseptically failed joint prostheses on osteoblast cultures.
Synovial fluid samples were obtained from patients with failed total joint prostheses (TJP; n=36) and from control patient groups (n = 16) involving cases without TJP and osteoarthritis, without TJP but with osteoarthritis, and with stable TJP. The samples were treated in the standard manner and then cultured with the SaOS-2 cell line which shows the characteristics and behaviour of osteoblasts. Each fluid sample was also examined for the content of proteins, cells and selected cytokines (IL-1ß, TNF-α, IL-6, RANKL and OPG detected by ELISA). We tested the hypothesis assuming that the fluids from failed joints would show higher cytotoxicity to osteoblast culture and we also expected higher levels of IL-1ß, TNF-α, IL-6, and RANKL in patients with TJP failure and/ or with more severe bone loss. The statistical methods used included the Kruskal-Wallis ANOVA and Mann-Whitney U test.
The fluids from failed TJPs showed the highest RANKL and the lowest OPG levels resulting in the highest RANKL/OPG ratio. However, there was no evidence suggesting that the joint fluids from failed TJPs would be more toxic to osteoblast culture than the fluids from control groups. In addition, no correlation was found between the fluid levels of molecules promoting inflammation and osteoclastic activity and the extent of bone loss in the hip (in terms of Saleh's classification) or the knee (AORI classification). In fact, the fluids from failed TJPs had higher protein levels in comparison with the controls, but the difference was not significant.
The finding of high RANKL levels and low OPG concentrations is in agreement with the theory of aseptic loosening and periprosthetic osteolysis. The other cytokines, particularly TNF-α and IL-1ß, were found in low levels. This can be explained by the stage of particle disease at which the samples were taken for ELISA analysis. It is probable that the level of signal molecules reflects osteolytic process activity and is therefore not constant. The reason for no correlation found between cytokine levels and the extent of bone loss may also lie in the use of therapeutic classifications of bone defects that is apparently less sensitive to the biological activity of aseptic loosening and/or periprosthetic osteolysis.
Synovial fluids from failed total hip or knee joint prostheses are not toxic to osteoblast cultures. Cytotoxicity indicators and levels of pro-inflammatory and pro-osteoclastic cytokines (IL-1ß, TNF-α, IL-6, RANKL and OPG) do not correlate well with the extent of periprosthetic bone loss. Key words: total joint replacement, arthroplasty, aseptic loosening, periprosthetic osteolysis, joint fluid, SaOS-2 cell line, cytotoxicity, cytokines, RANKL, OPG.
全髋关节或膝关节置换术失败与关节液生成增加有关。关节液中含有磨损颗粒、宿主细胞和蛋白质,被认为与无菌性松动和假体周围骨溶解的发病机制有关。本研究调查了无菌性关节假体失败患者的滑液对成骨细胞培养的影响。
从全关节置换术失败的患者(TJP;n = 36)以及对照组患者(n = 16)获取滑液样本,对照组包括没有全关节置换术且无骨关节炎的患者、没有全关节置换术但患有骨关节炎的患者以及全关节置换术稳定的患者。样本采用标准方式处理,然后与表现出成骨细胞特征和行为的SaOS-2细胞系进行培养。还对每个滑液样本的蛋白质、细胞含量以及选定的细胞因子(通过ELISA检测IL-1β、TNF-α、IL-6、RANKL和OPG)进行了检测。我们检验了这样的假设,即认为来自失败关节的滑液对成骨细胞培养具有更高的细胞毒性,并且我们还预期在全关节置换术失败和/或骨丢失更严重的患者中,IL-1β、TNF-α、IL-6和RANKL水平会更高。所使用的统计方法包括Kruskal-Wallis方差分析和Mann-Whitney U检验。
失败的全关节置换术患者的滑液显示出最高的RANKL水平和最低的OPG水平,导致RANKL/OPG比值最高。然而,没有证据表明失败的全关节置换术患者的关节液比对照组的滑液对成骨细胞培养更具毒性。此外,在促进炎症和破骨细胞活性的分子的滑液水平与髋关节(根据Saleh分类)或膝关节(AORI分类)的骨丢失程度之间未发现相关性。实际上,与对照组相比,失败的全关节置换术患者的滑液蛋白质水平更高,但差异不显著。
RANKL水平高而OPG浓度低的发现与无菌性松动和假体周围骨溶解的理论一致。其他细胞因子,特别是TNF-α和IL-1β,水平较低。这可以通过用于ELISA分析的样本所取自的颗粒疾病阶段来解释。信号分子的水平可能反映了骨溶解过程的活性,因此不是恒定的。细胞因子水平与骨丢失程度之间未发现相关性的原因也可能在于使用的骨缺损治疗分类对无菌性松动和/或假体周围骨溶解的生物学活性明显不敏感。
失败的全髋关节或膝关节假体的滑液对成骨细胞培养无毒。细胞毒性指标以及促炎和促破骨细胞细胞因子(IL-1β、TNF-α、IL-6、RANKL和OPG)的水平与假体周围骨丢失程度相关性不佳。关键词:全关节置换、关节成形术、无菌性松动、假体周围骨溶解、关节液、SaOS-2细胞系、细胞毒性、细胞因子、RANKL、OPG