代表性生物标记物及MicroRNAs在骨关节炎诊断及病情评估中的意义

Serum biomarkers and micro RNAs for diagnosis and progression assessment of osteoarthritis

[目的]通过检测不同软骨退变程度的患者的关节组织转换生物标记物及血清Micro RNAs,评估其对骨性关节炎的诊断价值。[方法]选取2015年1月~2015年5月于本院行膝关节镜手术或初次人工膝关节置换术的患者44例。术前留取血清、尿、关节液标本。测定s-CTX-I、u-CTX-I、u-CTX-II、sf-CTX-II、s-COMP、u-COMP、sf-COMP、s-HA、sf-HA值,同时测定血清mi R-885-5p、mi R-let-7e、mi R-140-3p、mi R-28-3p及mi R-454的量。评估各生物标记物的量与不同患者K-L分级、Outerbridge分级之间的相关性。并根据K-L分级,分成r OA组(影像学OA改变组,radiological osteoarthritis,r OA)(K-L分级≥2级)及非r OA组(K-L分级<2级),比较两组中生物标记物含量的差异。同时记录两组患者的性别、年龄、身高、体重,分析各生物标记物的影响因素。[结果]在测定的9项生物指标中,仅s-CTX-I、s-COMP、s-HA的含量与K-L分级及Outerbridge评分呈正相关,其余6项未见明显相关性。r OA组s-CTX-I、s-COMP、s-HA的含量分别为(270.40±52.01)pg/ml、(227.10±71.82)ng/ml、(14.11±5.53)ng/ml,显著高于非r OA组,后者分别为(230.22±38.15)pg/ml、(176.44±40.66)ng/ml、(9.06±2.76)ng/ml(P<0.05),其余6项生物标记物含量未见明显差异。血清mi R-885-5p、mi R-let-7e、mi R-140-3p、mi R-28-3p及mi R-454的相对表达量随着K-L分级逐渐增高,但与K-L分级及Outerbidge分级均无明显相关性。[结论]血清CTX-I、COMP及HA的含量在OA诊断及病情评估中具有一定的意义,但易受其他代谢状态、性别及年龄的影响。Micro RNAs能反映软骨转换状态,但对于OA的诊断价值仍需进一步明确。

[Objective] To investigate the value of joint tissue turnover biomarkers and serum MieroRNAs in diagnosing and clinical progression assessing of osteoarthritis by testing patients with varying degrees of articulation-cartilage degeneration. [Methods ] Forty-four patients with a diagnosis of osteoarthritis underwent knee arthroscopy or total knee arthroplasty in Pcking University First Hospital between January and May 2015. The serum （s） , urine （u） and synovial fluid （sf） samples were collected before surgery, s-CTX-I, u-CTX-I, u-CTX-II, sf-CTX-II, s-COMP, u-COMP, sf-COMP, s-HA and sf-HA of these samples were measured. The serum relative expression quantity of miR-885-Sp, miR-let-7e, miR-140-3p, miR-28-3p and miR-454 were measured as well. Then, the correlations between biomarkers and K-L grade, maximum Out- erhridge Score were analyzed. According to the results of K-L grade, patients were divided into radiographic knee osteoarthritis （rOA） group （K-L grade 2-4） and non-radiogTaphic knee osteoarthritis （non-rOA） group （K-L grade 0-1 ）, and the differenees of the biomarkers＇ concentrations between the two groups were compared. The patient＇ s gender, age, height, weight and diagnosis were recorded tbr analyzing the influence factors of these biomarkers. [Results] There were positive correlations between the concentrations of s-CTX- I, s-COMP, s-HA and K-L grade, as well as maximum Outerbridge Score. The concentrations of s-CTX-I, s- COMP, s-HA in tile rOA group, showed （270.40±52.01）pg/mL, （227.10±71.82） ng/mL, （14.11±5.53） ng/mL respectively were significantly higher than those in the non-rOA group （p〈0.05）, the lattereoncentrationswere （230.22±38.15） pg/mL, （176.44±40.66） ng/mLand （9.06±2.76） ng/mL. The serum relative expression quantity of miR-885-5p, miR-let-7e, miR-140-3p, miR-28-3p, miR-454 were consis- tently elevated with K-L grade, but the relative expression quantity showed no correlations with K-L grade and maximum Outerbridge Score. [Conelusion] The serum concentrations of CTX-I, COMP and HA have a certain significance in the diagno- sis and evaluation,of osteoarthritis, hut they are easily affected by other metabolic status, gender and age. MieroRNAs may refleet the cartilage iturnover status, and it needs further investigation to clarify the value of OA diagnosis.