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Arch Oral Biol. 2016 Sep;69:47-62. doi: 10.1016/j.archoralbio.2016.05.007. Epub 2016 May 14.

Malocclusion model of temporomandibular joint osteoarthritis in mice with and without receptor for advanced glycation end products.

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Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
Department of Statistics, Brigham Young University, Provo, UT 84602, USA.
Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA. Electronic address:



This study has two aims: 1. Validate a non-invasive malocclusion model of mouse temporomandibular joint (TMJ) osteoarthritis (OA) that we developed and 2. Confirm role of inflammation in TMJ OA by comparing the disease in the presence and absence of the receptor for advanced glycation end products (RAGE).


The malocclusion procedure was performed on eight week old mice, either wild type (WT) or without RAGE.


We observed TMJ OA at two weeks post-misalignment/malocclusion. The modified Mankin score used for the semi-quantitative assessment of OA showed an overall significantly higher score in mice with malocclusion compared to control mice at all times points (2, 4, 6 and 8 weeks). Mice with malocclusion showed a decrease in body weight by the first week after misalignment but returned to normal weight for their ages during the following weeks. The RAGE knock out (KO) mice had statistically lower modified Mankin scores compared to WT mice of the same age. The RAGE KO mice had statistically lower levels of Mmp-13 and HtrA1 but higher Tgf-β1, as measured by immunohistochemistry, compared to WT mice at eight weeks post malocclusion.


We demonstrate an inexpensive, efficient, highly reproducible and non-invasive model of mouse TMJ OA. The mechanical nature of the malocclusion resembles the natural development of TMJ OA in humans, making this an ideal model in future studies that aim to elucidate the pathogenesis of the disease leading to the discovery of a treatment. The RAGE plays a role in mouse TMJ OA.


Malocclusion; Mouse; Osteoarthritis; RAGE; Temporomandibular joint

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