Xie Zikun, Aitken Dawn, Liu Ming, Lei Guanghua, Jones Graeme, Cicuttini Flavia, Zhai Guangju
Division of Biomedical Sciences (Genetics), Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL A1B 3V6, Canada.
Xiangya Hospital, Central South University, Changsha 410008, China.
Life (Basel). 2022 Jun 10;12(6):869. doi: 10.3390/life12060869.
Osteoarthritis (OA) is the most prevalent joint disorder characterized by joint structural pathological changes with the loss of articular cartilage as its hallmark. Tools that can predict cartilage loss would help identify people at high risk, thus preventing OA development. The recent advance of the metabolomics provides a new avenue to systematically investigate metabolic alterations in disease and identify biomarkers for early diagnosis. Using a metabolomics approach, the current study aimed to identify serum metabolomic signatures for predicting knee cartilage volume loss over 10 years in the Tasmania Older Adult Cohort (TASOAC). Cartilage volume was measured in the medial, lateral, and patellar compartments of the knee by MRI at baseline and follow-up. Changes in cartilage volume over 10 years were calculated as percentage change per year. Fasting serum samples collected at 2.6-year follow-up were metabolomically profiled using the TMIC Prime Metabolomics Profiling Assay and pairwise metabolite ratios as the proxies of enzymatic reaction were calculated. Linear regression was used to identify metabolite ratio(s) associated with change in cartilage volume in each of the knee compartments with adjustment for age, sex, and BMI. The significance level was defined at α = 3.0 × 10−6 to control multiple testing. A total of 344 participants (51% females) were included in the study. The mean age was 62.83 ± 6.13 years and the mean BMI was 27.48 ± 4.41 kg/m2 at baseline. The average follow-up time was 10.84 ± 0.66 years. Cartilage volume was reduced by 1.34 ± 0.72%, 1.06 ± 0.58%, and 0.98 ± 0.46% per year in the medial, lateral, and patellar compartments, respectively. Our data showed that the increased ratios of hexadecenoylcarnitine (C16:1) to tetradecanoylcarnitine (C14) and C16:1 to dodecanoylcarnitine (C12) were associated with 0.12 ± 0.02% reduction per year in patellar cartilage volume (both p < 3.03 × 10−6). In conclusion, our data suggested that alteration of long chain fatty acid β-oxidation was involved in patellar cartilage loss. While confirmation is needed, the ratios of C16:1 to C14 and C12 might be used to predict long-term cartilage loss.
骨关节炎（OA）是最常见的关节疾病，其特征是关节结构发生病理变化，以关节软骨丧失为标志。能够预测软骨丧失的工具将有助于识别高危人群，从而预防骨关节炎的发展。代谢组学的最新进展为系统研究疾病中的代谢变化和识别早期诊断的生物标志物提供了一条新途径。本研究采用代谢组学方法，旨在识别塔斯马尼亚老年人群队列（TASOAC）中预测10年内膝关节软骨体积丧失的血清代谢组学特征。在基线和随访时通过MRI测量膝关节内侧、外侧和髌股关节腔的软骨体积。计算10年内软骨体积的变化，以每年的百分比变化表示。使用TMIC Prime代谢组学分析方法对在2.6年随访时采集的空腹血清样本进行代谢组学分析，并计算成对代谢物比率作为酶促反应的替代指标。采用线性回归分析确定与每个膝关节腔软骨体积变化相关的代谢物比率，并对年龄、性别和体重指数进行校正。显著性水平定义为α = 3.0 × 10−6以控制多重检验。共有344名参与者（51%为女性）纳入本研究。基线时平均年龄为62.83 ± 6.13岁，平均体重指数为27.48 ± 4.41 kg/m2。平均随访时间为10.84 ± 0.66年。内侧、外侧和髌股关节腔的软骨体积每年分别减少1.34 ± 0.72%、1.06 ± 0.58%和0.98 ± 0.46%。我们的数据表明，十六碳烯酰肉碱（C16:1）与十四烷酰肉碱（C14）以及C16:1与十二烷酰肉碱（C12）的比率增加与髌股软骨体积每年减少0.12 ± 0.02%相关（两者p < 3.03 × 10−6）。总之，我们的数据表明长链脂肪酸β氧化的改变与髌股软骨丧失有关。虽然需要进一步证实，但C16:1与C14和C12的比率可能用于预测长期软骨丧失。
