title: Osteoarthritis in temporomandibular joint of Col2a1 mutant mice.
abstract: OBJECTIVE
  Col2a1 gene mutations cause premature degeneration of knee articular cartilage in disproportionate micromelia (Dmm) and spondyloepiphesial dysplasia congenita (sedc) mice. The present study analyses the temporomandibular joint (TMJ) in Col2a1 mutant mice in order to provide an animal model of TMJ osteoarthritis (OA) that may offer better understanding of the progression of this disease in humans.
  
  
  METHODS
  Dmm/+ mice and controls were compared at two, six, nine and 12 months. Craniums were fixed, processed to paraffin sections, stained with Safranin-O/Fast Green, and analysed with light microscopy. OA was quantified using a Mankin scoring procedure. Unfolded protein response (UPR) assay was performed and immunohistochemistry (IHC) was used to assay for known OA biomarkers.
  
  
  RESULTS
  Dmm/+ TMJs showed fissuring of condylar cartilage as early as 6 months of age. Chondrocytes were clustered, leaving acellular regions in the matrix. Significant staining of HtrA1, Ddr2 and Mmp-13 was observed in Dmm/+ mice (p<0.01). We detected upregulation of the UPR in knee but not TMJ.
  
  
  CONCLUSIONS
  Dmm/+ mice are subject to early-onset OA in the TMJ. We observed upregulation of biomarkers and condylar cartilage degradation concomitant with OA. An upregulated UPR may exacerbate the onset of OA. The Dmm/+ mouse TMJ is a viable model for the study of the progression of OA in humans.
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Ricks
authors.forename: J T
authors.initials: JT
authors.lastname: Farrell
authors.forename: D J
authors.initials: DJ
authors.lastname: Falk
authors.forename: D W
authors.initials: DW
authors.lastname: Holt
authors.forename: M
authors.initials: M
authors.lastname: Rees
authors.forename: J
authors.initials: J
authors.lastname: Carr
authors.forename: T
authors.initials: T
authors.lastname: Williams
authors.forename: B A
authors.initials: BA
authors.lastname: Nichols
authors.forename: L C
authors.initials: LC
authors.lastname: Bridgewater
authors.forename: P R
authors.initials: PR
authors.lastname: Reynolds
authors.forename: D L
authors.initials: DL
authors.lastname: Kooyman
authors.forename: R E
authors.initials: RE
authors.lastname: Seegmiller
mesh_terms: D017668:Age of Onset; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002356:Cartilage / Q000166:cytology* / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D000074289:High-Temperature Requirement A Serine Peptidase 1; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D013704:Temporomandibular Joint / Q000503:physiopathology*; D013705:Temporomandibular Joint Disorders / Q000235:genetics* / Q000378:metabolism; D056811:Unfolded Protein Response
chemical_list: D015415:Biomarkers; D024043:Collagen Type II; D011509:Proteoglycans; D000074289:High-Temperature Requirement A Serine Peptidase 1; C492073:HtrA1 protein, mouse; D012697:Serine Endopeptidases; D053509:Matrix Metalloproteinase 13
keywords: Col2a1; Ddr2; Disproportionate micromelia (Dmm); Osteoarthritis; Temporomandibular joint