Satake Yoshihiko, Takahashi Kenji, Saito Mitsuru, Takai Shinro
Department of Orthopaedic Surgery, Nippon Medical School.
Department of Orthopaedic Surgery, Jikei University School of Medicine.
J Nippon Med Sch. 2018;85(3):157-165. doi: 10.1272/jnms.JNMS.2018_85-23.
Aging is a primary risk factor for the development of osteoarthritis (OA). Recently, advanced glycation end products (AGEs) have received much attention in relation to aging and OA. Some AGEs are reported to be brownish, but the association between AGE levels and browning in articular cartilage is unknown. The purposes of this study were first, to develop a colorimetric device to evaluate the quality and aging of the articular cartilage, and second, to investigate the relationship between AGE levels and color of articular cartilage by using this device without enzymatic digestion of the articular surface.
Open-label, single-center, prospective study Methods: Seven patients with OA (1 man, 6 women; mean age, 74.4 years; age range 58-81 years) who underwent primary total knee arthroplasty at our university hospital between July and December 2014 were enrolled in the study. Articular cartilage was harvested from the femur and tibia during surgery. The color and chromaticity of the articular cartilage was assayed by using a newly developed device with high validity. The characteristics of the articular cartilage were examined using the CIE XYZ Color Coordinate System (International Commission on Illumination, Vienna, Austria), and the color indicative of browning of the cartilage was defined on the X- and Y-axes. The brightness was adjusted and the specimen was photographed submerged in distilled water and the color was measured using a commercial luminance and color analyzer. Measurement of X and Y was repeated 3 times per site at 9 different points on the articular cartilage surface, and the mean value per specimen was calculated. Pentosidine (a well characterized biomarker of AGEs) levels and hydroxyproline content in articular cartilage were determined by high-performance liquid chromatography (HPLC). The correlation between age, articular cartilage AGE levels, and browning was analyzed using Spearman's rank correlation coefficient. The association between the degree of macroscopic degeneration and AGE levels was analyzed using one-way analysis of variance.
Age was positively correlated with pentosidine levels in articular cartilage (r=0.322) and browning of articular cartilage (r=0.261). However, a weak negative correlation was observed between pentosidine levels and browning of articular cartilage (r=-0.564, p=0.004). No positive relationship was observed between pentosidine levels and browning of articular cartilage in the visible spectrum.
This study developed an original colorimetric device with high validity. Browning of articular cartilage increased with age, but this study did not detect pentosidine-caused browning. Further study is needed to clarify the factors associated with browning of cartilage.
衰老为骨关节炎（OA）发生发展的主要风险因素。近来，晚期糖基化终末产物（AGEs）在衰老及骨关节炎方面备受关注。有报道称部分AGEs呈褐色，但关节软骨中AGE水平与褐变之间的关联尚不清楚。本研究目的一是研发一种比色装置以评估关节软骨的质量及老化情况，二是使用该装置在不进行关节表面酶消化的情况下研究关节软骨中AGE水平与颜色之间的关系。
开放标签、单中心、前瞻性研究
选取2014年7月至12月在我校医院接受初次全膝关节置换术的7例骨关节炎患者（1例男性，6例女性；平均年龄74.4岁；年龄范围58 - 81岁）纳入研究。术中从股骨和胫骨获取关节软骨。使用新研发的具有高有效性的装置检测关节软骨的颜色和色度。采用CIE XYZ颜色坐标系（奥地利维也纳国际照明委员会）检查关节软骨的特征，并在X轴和Y轴上定义软骨褐变的颜色。调整亮度后，将标本置于蒸馏水中拍照，并使用商用亮度和颜色分析仪测量颜色。在关节软骨表面的9个不同点，每个部位重复测量X和Y 3次，并计算每个标本的平均值。采用高效液相色谱法（HPLC）测定关节软骨中戊糖苷（一种特征明确的AGEs生物标志物）水平和羟脯氨酸含量。使用Spearman等级相关系数分析年龄、关节软骨AGE水平与褐变之间的相关性。采用单因素方差分析分析宏观退变程度与AGE水平之间的关联。
年龄与关节软骨中戊糖苷水平（r = 0.322）及关节软骨褐变（r = 0.261）呈正相关。然而，戊糖苷水平与关节软骨褐变之间观察到弱负相关（r = -0.564，p = 0.004）。在可见光谱中，未观察到戊糖苷水平与关节软骨褐变之间存在正相关关系。
本研究研发出一种具有高有效性的原创比色装置。关节软骨褐变随年龄增加，但本研究未检测到戊糖苷引起的褐变。需要进一步研究以阐明与软骨褐变相关的因素。
