Georgiev Georgi P, Yordanov Yordan, Gaydarski Lyubomir, Tubbs Richard Shane, Olewnik Łukasz, Zielinska Nicol, Piagkou Maria, Ananiev Julian, Dimitrova Iva N, Slavchev Svetoslav A, Terziev Ivan, Suwannakhan Athikhun, Landzhov Boycho
Department of Orthopedics and Traumatology, University Hospital Queen Giovanna-ISUL, Medical University of Sofia, 1527 Sofia, Bulgaria.
Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
Biomedicines. 2024 Mar 15;12(3):659. doi: 10.3390/biomedicines12030659.
The human knee is a complex joint that comprises several ligaments, including the medial collateral ligament (MCL). The MCL provides stability to the knee and helps prevent its excessive inward movement. The MCL also has a thin layer of connective tissue known as the epiligament (EL), which adheres to the ligament. This unique feature has drawn attention in the field of ligament healing research, as it may have implications for the recovery process of MCL injuries. According to the EL theory, ligament regeneration relies heavily on the provision of cells, blood vessels, and molecules. The present study sought to compare the expression of vascular endothelial growth factor (VEGF), CD34, and α-smooth muscle actin (α-SMA) in healthy knees' proximal and distal MCL segments to better understand how these proteins affect ligament healing. By improving the EL theory, the current results could lead to more effective treatments for ligament injury. To conduct the present analysis, monoclonal antibodies were used against CD34, α-SMA, and VEGF to examine samples from 12 fresh knee joints' midsubstance MCLs. We identified a higher cell density in the EL than in the ligament connective tissue, with higher cell counts in the distal than in the proximal EL part. CD34 immunostaining was weak or absent in blood vessels and the EL, while α-SMA immunostaining was strongest in smooth muscle cells and the EL superficial layer. VEGF expression was mainly in the blood vessels' tunica media. The distal part showed more SMA-positive microscopy fields and higher cell density than the proximal part (4735 vs. 2680 cells/mm). Our study identified CD34, α-SMA, and VEGF expression in the MCL EL, highlighting their critical role in ligament healing. Differences in α-SMA expression and cell numbers between the ligament's proximal and distal parts may explain different healing capacities, supporting the validity of the EL theory in ligament recovery.
人类膝关节是一个复杂的关节，由多条韧带组成，包括内侧副韧带（MCL）。内侧副韧带为膝关节提供稳定性，并有助于防止其过度向内移动。内侧副韧带还有一层薄薄的结缔组织，称为韧带外层（EL），它附着在韧带上。这一独特特征在韧带愈合研究领域引起了关注，因为它可能对内侧副韧带损伤的恢复过程有影响。根据韧带外层理论，韧带再生在很大程度上依赖于细胞、血管和分子的供应。本研究旨在比较健康膝关节内侧副韧带近端和远端节段中血管内皮生长因子（VEGF）、CD34和α平滑肌肌动蛋白（α-SMA）的表达，以更好地了解这些蛋白质如何影响韧带愈合。通过完善韧带外层理论，目前的研究结果可能会带来更有效的韧带损伤治疗方法。为了进行本分析，使用针对CD34、α-SMA和VEGF的单克隆抗体来检测来自12个新鲜膝关节内侧副韧带中间部分的样本。我们发现韧带外层的细胞密度高于韧带结缔组织，远端韧带外层的细胞数量高于近端。血管和韧带外层中CD34免疫染色较弱或无染色，而α-SMA免疫染色在平滑肌细胞和韧带外层表层最强。VEGF表达主要在血管中膜。远端部分比近端部分显示更多的SMA阳性显微镜视野和更高的细胞密度（4735个细胞/mm对2680个细胞/mm）。我们的研究确定了内侧副韧带韧带外层中CD34、α-SMA和VEGF的表达，突出了它们在韧带愈合中的关键作用。韧带近端和远端部分α-SMA表达和细胞数量的差异可能解释了不同的愈合能力，支持韧带外层理论在韧带恢复中的有效性。
