Decoding the mechanical characteristics of the human anterior cruciate ligament entheses through graduated mineralization interfaces

Jinghua Fang, Xiaozhao Wang, Huinan Lai, Wenyue Li, Xudong Yao, Zongyou Pan, Renwei Mao, Yiyang Yan, Chang Xie, Junxin Lin, Wei Sun, Rui Li, Jiajie Wang, Jiacheng Dai, Kaiwang Xu, Xinning Yu, Tengjing Xu, Wangping Duan, Jin Qian (), Hongwei Ouyang () and Xuesong Dai ()
Additional contact information
Jinghua Fang: Zhejiang University
Xiaozhao Wang: Zhejiang University
Huinan Lai: Zhejiang University
Wenyue Li: Zhejiang University
Xudong Yao: Zhejiang University
Zongyou Pan: Zhejiang University
Renwei Mao: The Hong Kong Polytechnic University
Yiyang Yan: Zhejiang University
Chang Xie: Zhejiang University
Junxin Lin: Zhejiang University
Wei Sun: Zhejiang University
Rui Li: Zhejiang University
Jiajie Wang: Zhejiang University
Jiacheng Dai: Zhejiang University
Kaiwang Xu: Zhejiang University
Xinning Yu: Zhejiang University
Tengjing Xu: Zhejiang University
Wangping Duan: Second Hospital of Shanxi Medical University
Jin Qian: Zhejiang University
Hongwei Ouyang: Zhejiang University
Xuesong Dai: Zhejiang University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-53542-5

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