title: 3D osteoarthritic changes in TMJ condylar morphology correlates with specific systemic and local biomarkers of disease.
abstract: OBJECTIVE
  To assess 3D morphological variations and local and systemic biomarker profiles in subjects with a diagnosis of temporomandibular joint osteoarthritis (TMJ OA).
  
  
  METHODS
  Twenty-eight patients with long-term TMJ OA (39.9 ± 16 years), 12 patients at initial diagnosis of OA (47.4 ± 16.1 years), and 12 healthy controls (41.8 ± 12.2 years) were recruited. All patients were female and had cone beam CT scans taken. TMJ arthrocentesis and venipuncture were performed on 12 OA and 12 age-matched healthy controls. Serum and synovial fluid levels of 50 biomarkers of arthritic inflammation were quantified by protein microarrays. Shape Analysis MANCOVA tested statistical correlations between biomarker levels and variations in condylar morphology.
  
  
  RESULTS
  Compared with healthy controls, the OA average condyle was significantly smaller in all dimensions except its anterior surface, with areas indicative of bone resorption along the articular surface, particularly in the lateral pole. Synovial fluid levels of ANG, GDF15, TIMP-1, CXCL16, MMP-3 and MMP-7 were significantly correlated with bone apposition of the condylar anterior surface. Serum levels of ENA-78, MMP-3, PAI-1, VE-Cadherin, VEGF, GM-CSF, TGFβb1, IFNγg, TNFαa, IL-1αa, and IL-6 were significantly correlated with flattening of the lateral pole. Expression levels of ANG were significantly correlated with the articular morphology in healthy controls.
  
  
  CONCLUSIONS
  Bone resorption at the articular surface, particularly at the lateral pole was statistically significant at initial diagnosis of TMJ OA. Synovial fluid levels of ANG, GDF15, TIMP-1, CXCL16, MMP-3 and MMP-7 were correlated with bone apposition. Serum levels of ENA-78, MMP-3, PAI-1, VE-Cadherin, VEGF, GM-CSF, TGFβ1, IFNγ, TNFα, IL-1α, and IL-6 were correlated with bone resorption.
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI, USA. Electronic address: luciacev@umich.edu.
authors.forename: L H S
authors.initials: LH
authors.lastname: Cevidanes
authors.affiliation: Department of Orthodontics, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: D
authors.initials: D
authors.lastname: Walker
authors.affiliation: Department of Periodontics and Oral Medicine School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: J
authors.initials: J
authors.lastname: Schilling
authors.affiliation: Department of Periodontics and Oral Medicine School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: J
authors.initials: J
authors.lastname: Sugai
authors.affiliation: Department of Periodontics and Oral Medicine School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: W
authors.initials: W
authors.lastname: Giannobile
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: B
authors.initials: B
authors.lastname: Paniagua
authors.affiliation: Department of Periodontics and Oral Medicine School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: E
authors.initials: E
authors.lastname: Benavides
authors.affiliation: Department of Statistics, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Statistics, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Marron
authors.affiliation: Department of Statistics, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: B T
authors.initials: BT
authors.lastname: Jung
authors.affiliation: Department of Orthodontics, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: D
authors.initials: D
authors.lastname: Baranowski
authors.affiliation: Department of Endodontics, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rhodes
authors.affiliation: Department of Endodontics, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: A
authors.initials: A
authors.lastname: Nackley
authors.affiliation: Department of Endodontics, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Lim
authors.affiliation: Department of Diagnostic Sciences, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Ludlow
authors.affiliation: Department of Orthodontics, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: T
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Department of Pediatric Dentistry, State University of Sao Paulo, Araraquara, Brazil.
authors.forename: J R
authors.initials: JR
authors.lastname: Goncalves
authors.affiliation: Department of Oral Maxillofacial Surgery, Baylor College of Dentistry, Dallas, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wolford
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kapila
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: M
authors.initials: M
authors.lastname: Styner
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000209:etiology; D016022:Case-Control Studies; D054893:Cone-Beam Computed Tomography; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D018836:Inflammation Mediators / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000150:complications / Q000000981:diagnostic imaging*; D013582:Synovial Fluid / Q000378:metabolism*; D013704:Temporomandibular Joint / Q000000981:diagnostic imaging*; D013705:Temporomandibular Joint Disorders / Q000150:complications / Q000000981:diagnostic imaging*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators
keywords: Image analysis; Imaging biomarkers; Protein biomarkers