Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Orthopedics Research Institute of Zhejiang University, Hangzhou, China.
Nat Commun. 2024 Oct 26;15(1):9253. doi: 10.1038/s41467-024-53542-5.
The anterior cruciate ligament is anchored to the femur and tibia via specialized interfaces known as entheses. These play a critical role in ligament homeostasis and joint stability by transferring forces, varying in magnitude and direction between structurally and functionally dissimilar tissues. However, the precise structural and mechanical characteristics underlying the femoral and tibial entheses and their intricate interplay remain elusive. In this study, two thin-graduated mineralization regions in the femoral enthesis (21 μm) and tibial enthesis (14 μm) are identified, both exhibiting distinct biomolecular compositions and mineral assembly patterns. Notably, the femoral enthesis interface exhibits progressively maturing hydroxyapatites, whereas the mineral at the tibial enthesis interface region transitions from amorphous calcium phosphate to hydroxyapatites with increasing crystallinity. Proteomics results reveal that Matrix Gla protein uniquely enriched at the tibial enthesis interface, may stabilize amorphous calcium phosphate, while C-type lectin domain containing 11 A, enriched at the femoral enthesis interface, could facilitate the interface mineralization. Moreover, the finite element analysis indicates that the femoral enthesis model exhibited higher resistance to shearing, whereas the tibial enthesis model contributes to tensile resistance, suggesting that the discrepancy in biomolecular expression and the corresponding mineral assembly heterogeneities collectively contribute to the superior mechanical properties of both the femoral enthesis and tibial enthesis models. These findings provide novel perspectives on the structure-function relationships of anterior cruciate ligament entheses, paving the way for improved management of anterior cruciate ligament injury and regeneration.
前交叉韧带通过称为附着点的专门界面固定在股骨和胫骨上。这些附着点通过传递大小和方向不断变化的力在韧带内稳态和关节稳定性中发挥着关键作用，这些力在结构和功能上与不同的组织不同。然而，股骨和胫骨附着点的精确结构和力学特性及其复杂的相互作用仍然难以捉摸。在这项研究中，确定了股骨附着点（约 21μm）和胫骨附着点（约 14μm）中的两个薄梯度矿化区域，两者均表现出不同的生物分子组成和矿物组装模式。值得注意的是，股骨附着点界面表现出逐渐成熟的羟基磷灰石，而在胫骨附着点界面区域的矿物质则从无定形磷酸钙转变为具有增加的结晶度的羟基磷灰石。蛋白质组学结果表明，富含在胫骨附着点界面的基质 Gla 蛋白可能稳定无定形磷酸钙，而富含在股骨附着点界面的 C 型凝集素结构域包含 11A 可能有助于界面矿化。此外，有限元分析表明，股骨附着点模型表现出更高的抗剪切能力，而胫骨附着点模型有助于抗拉伸，这表明生物分子表达和相应的矿物组装异质性的差异共同导致了股骨附着点和胫骨附着点模型的优异力学性能。这些发现为前交叉韧带附着点的结构-功能关系提供了新的视角，为前交叉韧带损伤和再生的更好管理铺平了道路。
