Department of Anesthesiology, Tri-Service General Hospital, Taipei 114202, Taiwan.
National Defense Medical Center, Graduate Institute of Medical Sciences, Taipei 114201, Taiwan.
Int J Mol Sci. 2021 Sep 22;22(19):10179. doi: 10.3390/ijms221910179.
Biomarkers are essential tools in osteoarthritis (OA) research, clinical trials, and drug development. Detecting and evaluating biomarkers in OA research can open new avenues for researching and developing new therapeutics. In the present report, we have explored the serological detection of various osteoarthritis-related biomarkers in the preclinical model of OA. In this surgical OA model, we disrupted the medial tibial cartilage's integrity via anterior cruciate ligament transection combined with medial meniscectomy (ACLT+MMx) of a single joint of Wistar rats. The progression of OA was verified, as shown by the microscopic deterioration of cartilage and the increasing cartilage degeneration scoring from 4 to 12 weeks postsurgery. The concentration of serological biomarkers was measured at two timepoints, along with the complete blood count and bone electrolytes, with biochemical analysis further conducted. The panel evaluated inflammatory biomarkers, bone/cartilage biomarkers, and lipid metabolic pathway biomarkers. In chronic OA rats, we found a significant reduction of total vitamin D3 and C-telopeptide fragments of type II (CTX-II) levels in the serum as compared to sham-operated rats. In contrast, the serological levels of adiponectin, leptin, and matrix metallopeptidase (MMP3) were significantly enhanced in chronic OA rats. The inflammatory markers, blood cell composition, and biochemical profile remained unchanged after surgery. In conclusion, we found that a preclinical model of single-joint OA with significant deterioration of the cartilage can lead to serological changes to the cartilage and metabolic-related biomarkers without alteration of the systemic blood and biochemical profile. Thus, this biomarker profile provides a new tool for diagnostic/therapeutic assessment in OA scientific research.
生物标志物是骨关节炎（OA）研究、临床试验和药物开发的重要工具。在 OA 研究中检测和评估生物标志物可以为研究和开发新的治疗方法开辟新的途径。在本报告中，我们探讨了在 OA 的临床前模型中检测各种与 OA 相关的生物标志物的血清学方法。在这种手术性 OA 模型中，我们通过前交叉韧带切断术联合内侧半月板切除术（ACLT+MMx）破坏了单个关节的 Wistar 大鼠的内侧胫骨软骨的完整性。通过手术后 4 至 12 周的软骨微观恶化和软骨退变评分的增加，验证了 OA 的进展。在两个时间点测量了血清生物标志物的浓度，同时还测量了全血细胞计数和骨电解质，并进行了生化分析。该小组评估了炎症生物标志物、骨/软骨生物标志物和脂质代谢途径生物标志物。在慢性 OA 大鼠中，与假手术大鼠相比，我们发现血清中的总维生素 D3 和 II 型胶原 C 端肽（CTX-II）水平显著降低。相比之下，慢性 OA 大鼠的血清中脂联素、瘦素和基质金属蛋白酶（MMP3）水平显著升高。手术后炎症标志物、血细胞组成和生化特征保持不变。总之，我们发现，具有软骨明显恶化的单关节 OA 的临床前模型可导致软骨和代谢相关生物标志物的血清学变化，而不会改变全身血液和生化特征。因此，这种生物标志物谱为 OA 科学研究中的诊断/治疗评估提供了一种新工具。
