title: Nanoindentation modulus of murine cartilage: a sensitive indicator of the initiation and progression of post-traumatic osteoarthritis.
abstract: This study aims to demonstrate that cartilage nanoindentation modulus is a highly sensitive indicator of the onset and spatiotemporal progression of post-traumatic osteoarthritis (PTOA) in murine models.
  
  
  
  Destabilization of the medial meniscus (DMM) surgery was performed on the right knees of 12-week old male, wild-type C57BL/6 mice, with Sham control on contralateral left knees. Atomic force microscopy (AFM)-based nanoindentation was applied to quantify the nanoindentation modulus, Eind, of femoral condyle cartilage at 3 days to 12 weeks after surgery. The modulus changes were compared against the timeline of histological OA signs. Meanwhile, at 8 weeks after surgery, changes in meniscus, synovium and subchondral bone were evaluated to reveal the spatial progression of PTOA.
  
  
  
  The modulus of medial condyle cartilage was significantly reduced at 1 week after DMM, preceding the histological OA signs, which only became detectable at 4-8 weeks after. This reduction is likely due to concomitantly elevated proteolytic activities, as blocking enzymatic activities in mice can attenuate this modulus reduction. In later OA, lateral condyle cartilage and medial meniscus also started to be weakened, illustrating the whole-organ nature of PTOA.
  
  
  
  This study underscores the high sensitivity of nanoindentation in examining the initiation, attenuation and progression of PTOA in murine models. Meanwhile, modulus changes highlight concomitant changes in lateral cartilage and meniscus during the advancement of OA.
authors: School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, United States.
authors: B
authors: B
authors: Doyran
authors: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China.
authors: W
authors: W
authors: Tong
authors: School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, United States.
authors: Q
authors: Q
authors: Li
authors: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Orthopaedic Surgery, School of Medicine, ShiHeZi University, ShiHeZi, Xinjiang 832000, PR China.
authors: H
authors: H
authors: Jia
authors: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, PR China.
authors: X
authors: X
authors: Zhang
authors: Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors: C
authors: C
authors: Chen
authors: Department of Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States.
authors: M
authors: M
authors: Enomoto-Iwamoto
authors: Department of Mechanical Engineering, University of Delaware, Newark, DE 19716, United States.
authors: X L
authors: XL
authors: Lu
authors: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States. Electronic address: qinling@mail.med.upenn.edu.
authors: L
authors: L
authors: Qin
authors: School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, United States. Electronic address: lh535@drexel.edu.
authors: L
authors: L
authors: Han
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006614:Hindlimb; D007596:Joints / Q000473:pathology; D008297:Male; D000072600:Meniscus / Q000293:injuries* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010003:Osteoarthritis / Q000209:etiology* / Q000473:pathology
keywords: Cartilage; Destabilization of the medial meniscus (DMM); Murine models; Nanoindentation; Post-traumatic osteoarthritis