title: The role of TGF-ß1 in osteoarthritis of the temporomandibular joint in two genetic mouse models.
abstract: OBJECTIVE
  The objective of this study is to elucidate osteoarthritis (OA) progression in the temporomandibular joint (TMJ) in two genetic mouse models by assessing the expression of an identified inflammatory marker associated with OA, viz., Tgf-ß1. This study provides mechanistic insight into disease progression based on the temporal expression of Tgf-ß1 in the TMJ.
  
  
  METHODS
  The two models included the heterozygous chondrodysplasia mutation (cho/+), a Coll11a1 mutation, and the autosomal semidominant disproportionate micromelia mutation (Dmm/+), a Col2a1 mutation. To determine OA status histologically, TMJs from each mutant were fixed, sectioned and stained with Safranin O to identify proteoglycans in condylar cartilage and counterstained with Fast Green. The extent of staining and onset of OA-like changes were quantified using the Modified Mankin scoring system. Using immunofluorescence, selected tissue sections of each genotype were stained for the presence of Tgf-ß1, HtrA1, and p-Smad2.
  
  
  RESULTS
  The results revealed Mankin scores of the condylar cartilage of both mutants that are consistent with established histopathological changes of OA. Immunofluorescence indicated increased expression of all three molecular markers and their co-localization within condylar chondrocytes of both mutants.
  
  
  CONCLUSIONS
  Elevated Tgf-ß1 expression in mutant condylar cartilage supports the hypothesis that this inflammatory mediator is mechanistically involved in the pathogenesis of TMJ OA. Compared to basal expression in control TMJs, the positive co-localized staining for Tgf-ß1, HtrA1, and p-Smad2 in both mutants demonstrates involvement of these molecules in the degradative pathway of OA. Tgf-ß1 therefore is a potential target for further study for the diagnosis and treatment of TMJ OA.
authors.affiliation: Brigham Young University, College of Life Sciences, Provo, UT, USA.
authors.forename: E
authors.initials: E
authors.lastname: Long
authors.affiliation: Roseman University of Health Sciences, College of Dental Medicine, South Jordan, UT, USA.
authors.forename: R
authors.initials: R
authors.lastname: Motwani
authors.affiliation: Roseman University of Health Sciences, College of Dental Medicine, South Jordan, UT, USA.
authors.forename: D
authors.initials: D
authors.lastname: Reece
authors.affiliation: Roseman University of Health Sciences, College of Dental Medicine, South Jordan, UT, USA.
authors.forename: N
authors.initials: N
authors.lastname: Pettit
authors.affiliation: Roseman University of Health Sciences, College of Dental Medicine, South Jordan, UT, USA.
authors.forename: J
authors.initials: J
authors.lastname: Hepworth
authors.affiliation: Roseman University of Health Sciences, College of Dental Medicine, South Jordan, UT, USA.
authors.forename: P
authors.initials: P
authors.lastname: Wong
authors.affiliation: Brigham Young University, College of Life Sciences, Provo, UT, USA.
authors.forename: P
authors.initials: P
authors.lastname: Reynolds
authors.affiliation: Roseman University of Health Sciences, College of Dental Medicine, South Jordan, UT, USA. Electronic address: rseegmiller@roseman.edu.
authors.forename: R
authors.initials: R
authors.lastname: Seegmiller
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D051379:Mice; D009154:Mutation; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010009:Osteochondrodysplasias / Q000378:metabolism / Q000473:pathology; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000378:metabolism; D051899:Smad2 Protein / Q000096:biosynthesis / Q000378:metabolism; D013704:Temporomandibular Joint / Q000378:metabolism* / Q000473:pathology; D013705:Temporomandibular Joint Disorders / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D011509:Proteoglycans; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D053773:Transforming Growth Factor beta1; D000074289:High-Temperature Requirement A Serine Peptidase 1; C492073:HtrA1 protein, mouse; D012697:Serine Endopeptidases
keywords: Chondrodysplasia (cho); Disproportionate micromelia (Dmm); Osteoarthritis (OA); Smad2; Temporomandibular joint (TMJ); Tgf-ß1