title: Identification of shoulder osteoarthritis biomarkers: comparison between shoulders with and without osteoarthritis.
abstract: BACKGROUND
  The biologic factors associated with shoulder osteoarthritis (OA) have not been elucidated. The purpose of this study was to investigate osteoarthritic biomarkers of the shoulder. To our knowledge, this is the first study to analyze shoulder cartilage for OA-associated genes and to examine human shoulder cartilage for a possible biomarker, connexin 43 (Cx43).
  
  
  METHODS
  Cartilage from 16 osteoarthritic and 10 nonosteoarthritic humeral heads was assessed for expression of the following genes by real-time polymerase chain reaction: types I, II, and X collagen; matrix metalloproteinases (MMPs); tissue inhibitors of MMP (TIMPs); interleukins; versican; cyclooxygenase 2 (Cox-2); inducible nitric oxide synthase (iNOS); tumor necrosis factor α (TNF-α); aggrecanase 2 (ADAMTS5); and Cx43.
  
  
  RESULTS
  In osteoarthritic shoulders, Cx43, Cox-2, versican, collagen type I, ADAMTS5, MMP-3, and TNF-α expressions were significantly increased compared with controls. TIMP-3 and iNOS trended toward significance, with robust expression in osteoarthritic shoulders and low expression in nonosteoarthritic shoulders. In osteoarthritic shoulders, gene expression of Cx43, ADAMTS5, collagen type I, Cox-2, versican, and TIMP-3 showed predominance (85-, 33-, 13-, 12-, 11.5-, and 3-fold increases, respectively) relative to nonosteoarthritic controls. Spearman correlation analysis showed significant correlations between Cx43 and collagen (types I, II, and X), MMP-9, TIMP-2 and TIMP-3, versican, Cox-2, iNOS, and ADAMTS5.
  
  
  CONCLUSIONS
  Certain genes are markedly upregulated in osteoarthritic shoulders compared with nonosteoarthritic shoulders, with Cx43, Cox-2, versican, collagen type I, ADAMTS5, MMP-3, and TNF-α expression being significantly increased. These genes might be useful biomarkers for examining shoulder OA.
  
  
  CONCLUSIONS
  Identification of osteoarthritic biomarkers can help us better understand shoulder OA and build the foundation for future research on disease progression and treatments.
authors.affiliation: Department of Orthopaedics, University of Maryland, Baltimore, MD, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Casagrande
authors.affiliation: Department of Orthopaedics, University of Maryland, Baltimore, MD, USA. Electronic address: jstains@umoa.umm.edu.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Stains
authors.affiliation: Department of Orthopaedics, University of Maryland, Baltimore, MD, USA.
authors.forename: Anand M
authors.initials: AM
authors.lastname: Murthi
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis; D000071116:ADAMTS5 Protein; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D002358:Cartilage, Articular / Q000737:chemistry*; D003094:Collagen / Q000096:biosynthesis; D018031:Connexin 43 / Q000032:analysis*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D005260:Female; D006801:Humans; D058430:Humeral Head / Q000737:chemistry*; D007378:Interleukins / Q000096:biosynthesis; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism*; D012785:Shoulder Joint / Q000737:chemistry*; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation; D053675:Versicans / Q000096:biosynthesis
chemical_list: D015415:Biomarkers; D018031:Connexin 43; C500216:GJA1 protein, human; D007378:Interleukins; D019714:Tissue Inhibitor of Metalloproteinases; D014409:Tumor Necrosis Factor-alpha; C508322:VCAN protein, human; D053675:Versicans; D003094:Collagen; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; D020782:Matrix Metalloproteinases
keywords: Shoulder; biomarkers; connexin 43; osteoarthritis