Knee immobilization reproduces key arthrofibrotic phenotypes in mice

Bone & Joint Research

article

Louis Dagneaux¹  Afton K. Limberg¹  Aaron R. Owen¹  Jacob W. Bettencourt¹  Amel Dudakovic¹  Banu Bayram¹  Naomi M. Gades²  Joaquin Sanchez-Sotelo¹  Daniel J. Berry¹  Andre van Wijnen¹  Mark E. Morrey¹  Matthew P. Abdel¹ 

[1]Department of Orthopedic Surgery, Mayo Clinic

[2]Department of Comparative Medicine, Mayo Clinic

关键词: Fibrosis;    Genetic predisposition;    Contracture;    Murine;    immobilization;    Knees;    contractures;    sutures;    mouse models;    extension angles;    Animal models;    histological analysis;    articular injury;    cartilage degeneration;   

DOI  :  10.1302/2046-3758.121.BJR-2022-0250.R2

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

AimsAs has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA).MethodsExperimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections.ResultsExperimental knees immobilized for four weeks demonstrated mean PEAs of 141°, 72°, and 79° after zero, two, and four weeks of remobilization (n = 6 per group), respectively. Experimental knees demonstrated reduced PEAs after two weeks (p < 0.001) and four weeks (p < 0.0001) of remobilization compared to controls. Following eight weeks of immobilization, experimental knees exhibited mean PEAs of 82°, 73°, and 72° after zero, two, and four weeks of remobilization, respectively. Histological analysis demonstrated no cartilage degeneration. Similar trends in biomechanical and histological properties were observed when intra-articular violation was introduced.ConclusionThis study established a novel mouse model of robust knee contracture without evidence of OA. This was appreciated consistently after eight weeks of immobilization and was irrespective of length of remobilization. As such, this arthrofibrotic model provides opportunities to investigate molecular pathways and therapeutic strategies.

【 授权许可】

CC BY-NC