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J Orthop Res. 2018 Mar;36(3):881-890. doi: 10.1002/jor.23712. Epub 2017 Sep 20.

Metabolic dysregulation accelerates injury-induced joint degeneration, driven by local inflammation; an in vivo rat study.

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Department of Orthopaedics, University Medical Center Utrecht, F.02.127, 3508 GA, Utrecht, 85500, The Netherlands.
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Metabolic Health Research, TNO, Leiden, The Netherlands.
Department of Biomechanical Engineering, Delft University of Technology, Delft, The Netherlands.


Evidence is growing for the existence of an obesity-related phenotype of osteoarthritis in which low-grade inflammation and a disturbed metabolic profile play a role. The contribution of an obesity-induced metabolic dysbalance to the progression of the features of osteoarthritis upon mechanically induced cartilage damage was studied in a rat in vivo model. Forty Wistar rats were randomly allocated 1:1 to a standard diet or a high-fat diet. After 12 weeks, in 14 out of 20 rats in each group, cartilage was mechanically damaged in the right knee joint. The remaining six animals in each group served as controls. After a subsequent 12 weeks, serum was collected for metabolic state, subchondral bone changes assessed by μCT imaging, osteoarthritis severity determined by histology, and macrophage presence assessed by CD68 staining. The high-fat diet increased statistically all relevant metabolic parameters, resulting in a dysmetabolic state and subsequent synovial inflammation, whereas cartilage degeneration was hardly influenced. The high-fat condition in combination with mechanical cartilage damage resulted in a clear statistically significant progression of the osteoarthritic features, with increased synovitis and multiple large osteophytes. Both the synovium and osteophytes contained numerous CD68 positive cells. It is concluded that a metabolic dysbalance due to a high-fat diet increases joint inflammation without cartilage degeneration. The dysmetabolic state clearly accelerates progression of osteoarthritis upon surgically induced cartilage damage supported by inflammatory responses as demonstrated by histology and increased CD68 expressing cells localized on the synovial membrane and osteophytes. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:881-890, 2018.


animal model; inflammation; metabolic syndrome; osteoarthritis; synovitis

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