Evaluation of enzymatic proteoglycan loss and collagen degradation in human articular cartilage using ultrashort echo time-based biomarkers: A feasibility study.
Evaluation of enzymatic proteoglycan loss and collagen degradation in human articular cartilage using ultrashort echo time-based biomarkers: A feasibility study.
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目的：探讨基于三维超短回波时间(UTE)的定量生物标志物检测人软骨蛋白多糖(PG)丢失和胶原降解的可行性。共采集104个软骨标本，分别进行胰酶消化研究(n=44)和胰酶及胶原酶连续消化研究(n=60)。将44例软骨标本随机分为胰酶消化组(Tryp组)和对照组(PBS组)，每组22例进行胰酶消化实验。其余60例软骨标本随机分为4组(每组15例)，PBS+Tris(PBS孵育，Tris缓冲液)，PBS+30U Col(PBS孵育，30U/ml胶原酶30U/ml Tris缓冲液孵育)，Tryp+30U Col(胰酶孵育，30U/ml胶原酶+Tris缓冲液)，Tryp+Tris(胰酶孵育，Tris缓冲液)。基于UTE的3DMRI生物标志物包括T1、多回声T2*、绝热T1ρ(ADIABT1ρ)、磁化转移率和大分子质子分数的模拟。对于每个软骨样本，在治疗前和治疗后评估基于UTE的生物标志物(T1、T2*、ADIABT1ρ、MTR和MMF)和样本重量。测定PG和羟脯氨酸含量。评估了不同组之间的差异和相关性。在胰酶消化实验中，所有被评估的生物标志物都能够区分健康和退变的软骨，但只有T1和AdiabT1ρ与消化液中PG浓度显著相关(p分别为0.004和0.0001)。在序贯消化实验中，硫代巴比妥钠+Tris组和硫代巴比妥钠+30U组之间的T1和AdiabT1ρ值无显著差异(p=0.627和0.877)，但t1和adabT1ρ值在Tryp+Tris组(p=0.031和0.024)和Tryp+30U组(P均为0.0001)中显著升高。TRYP+30U COOL组与PBS+TRIS组比较，MMF值和MTR值均显著降低(P分别为0.002和0.001)。AdiabT1、ρ和T1具有检测PG丢失的潜力，而MMF和MTR是检测关节软骨中胶原降解的有希望的方法，均有助于骨关节炎的早期、非侵入性诊断。
To investigate the feasibility of quantitative 3D ultrashort echo time (UTE)-based biomarkers in detecting proteoglycan (PG) loss and collagen degradation in human cartilage. A total of 104 cartilage samples were harvested for a trypsin digestion study (n=44), and a sequential trypsin and collagenase digestion study (n=60), respectively. 44 cartilage samples were randomly divided into a trypsin digestion group (tryp group) and a control group (PBS group) (n=22 for each group) for the trypsin digestion experiment. The remaining 60 cartilage samples were equally divided into four groups (n=15 for each group) for sequential trypsin and collagenase digestion, including PBS+Tris (incubated in PBS, then Tris buffer solution), PBS+30U col (incubated in PBS, then 30U/ml collagenase (30U col) with Tris buffer solution), tryp+30U col (incubated in trypsin solution, then 30U/ml collagenase with Tris buffer solution), and tryp+Tris (incubated in trypsin solution, then Tris buffer solution). The 3D UTE-based MRI biomarkers included T1, multi-echo T2*, adiabatic T1ρ (AdiabT1ρ), magnetization transfer ratio (MTR), and modeling of macromolecular proton fraction (MMF). For each cartilage sample, UTE-based biomarkers (T1, T2*, AdiabT1ρ, MTR, and MMF) and sample weight were evaluated before and after treatment. PG and hydroxyproline assays were performed. Differences between groups and correlations were assessed. All evaluated biomarkers were able to differentiate between healthy and degenerated cartilage in the trypsin digestion experiment, but only T1 and AdiabT1ρ were significantly correlated with the PG concentration in the digestion solution (p=0.004 and 0.0001, respectively). In the sequential digestion experiment, no significant differences were found for T1 and AdiabT1ρ values between PBS+Tris and PBS+30U col groups (p=0.627 and 0.877, respectively), but T1 and AdiabT1ρ values increased significantly in the tryp+Tris (p=0.031 and 0.024, respectively) and tryp+30U col groups (both p<0.0001). Significant decreases in MMF and MTR were found in the tryp+30U col group compared with the PBS+Tris group (p=0.002 and 0.001, respectively). AdiabT1ρ and T1 have the potential for detecting PG loss, while MMF and MTR are promising for the detection of collagen degradation in articular cartilage, which could all facilitate earlier, non-invasive diagnosis of osteoarthritis.
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