title: Malocclusion model of temporomandibular joint osteoarthritis in mice with and without receptor for advanced glycation end products.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  The malocclusion procedure was performed on eight week old mice, either wild type (WT) or without RAGE.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
authors.forename: E M Chávez
authors.initials: EM
authors.lastname: Matías
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Mecham
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Black
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Graf
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Steel
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Wilhelm
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Andersen
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Mitchell
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Macdonald
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
authors.forename: W R
authors.initials: WR
authors.lastname: Hollis
authors.affiliation: Department of Statistics, Brigham Young University, Provo, UT 84602, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Eggett
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Reynolds
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA. Electronic address: david_kooyman@byu.edu.
authors.forename: D L
authors.initials: DL
authors.lastname: Kooyman
mesh_terms: D000818:Animals; D017760:Bone Malalignment; D002358:Cartilage, Articular / Q000473:pathology; D019902:Chondrocytes / Q000473:pathology; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000378:metabolism; D000074289:High-Temperature Requirement A Serine Peptidase 1; D007150:Immunohistochemistry; D008310:Malocclusion / Q000473:pathology* / Q000503:physiopathology; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009969:Orthodontic Wires; D010003:Osteoarthritis / Q000473:pathology* / Q000503:physiopathology; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism; D013704:Temporomandibular Joint / Q000473:pathology*; D013705:Temporomandibular Joint Disorders / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D053773:Transforming Growth Factor beta1; D000074289:High-Temperature Requirement A Serine Peptidase 1; C492073:HtrA1 protein, mouse; D012697:Serine Endopeptidases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse
keywords: Malocclusion; Mouse; Osteoarthritis; RAGE; Temporomandibular joint