Effect of knee joint loading on chondrocyte mechano-vulnerability and severity of post-traumatic osteoarthritis induced by ACL-injury in mice

Osteoarthritis and Cartilage Open

卷:4

Can Nejat Yigit¹  Anissa Elahi²  Whasil Lee³  Ashley Proctor⁴  Alexander Kotelsky⁵  Sandeep Mannava⁵  Christoph Pröschel⁵ 

[1]Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA

[2]|Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY, USA

[3]|Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA

[4]|Department for Biomedical Genetics, University of Rochester, Rochester, NY, USA

[5]|Department of Biomedical Engineering, University of Rochester, NY, USA

关键词: Post-traumatic osteoarthritis (PT-OA);    Anterior cruciate ligament (ACL)-injury;    Chondrocyte death;    Extracellular matrix (ECM);    Gait analysis;   

DOI  :  

来源: DOAJ

【 摘 要 】

Objective: The objective of this study is to understand the role of altered in vivo mechanical environments in knee joints post anterior cruciate ligament (ACL)-injury in chondrocyte vulnerability against mechanical stimuli and in the progression of post-traumatic osteoarthritis (PT-OA). Methods: Differential in vivo mechanical environments were induced by unilateral ACL-injury (uni-ACL-I) and bilateral ACL-injury (bi-ACL-I) in 8-week-old female C57BL/6 mice. The gait parameters, the mechano-vulnerability of in situ chondrocytes, Young's moduli of cartilage extracellular matrix (ECM), and the histological assessment of OA severity (OARSI score) were compared between control and experimental groups at 0∼8-weeks post-ACL-injury. Results: We found that bi-ACL-I mice experience higher joint-loading on their both injured limbs, but uni-ACL-I mice balance their joint-loading between injured and uninjured hind limbs resulting in a reduced joint-loading during gait. We also found that at 4- and 8-week post-injury the higher weight-bearing hind limbs (i.e., bi-ACL-I) had the increased area of chondrocyte death induced by impact loading and higher OARSI score than the lower weight-bearing limbs (uni-ACL-I). Additionally, we found that at 8-weeks post-injury the ECM became stiffer in bi-ACL-I joints and softer in uni-ACL-I joints. Conclusions: Our results show that ACL-injured limbs with lower in vivo joint-loading develops PT-OA significantly slower than injured limbs with higher joint-loading during gait. Our data also indicate that articular chondrocytes in severe PT-OA are more fragile from mechanical impacts than chondrocytes in healthy or mild PT-OA. Thus, preserving physiologic joint-loads on injured joints will reduce chondrocyte death post-injury and may delay PT-OA progression.

【 授权许可】

Unknown