PMID- 25595362 OWN - NLM STAT- MEDLINE DCOM- 20150706 LR - 20181202 IS - 1532-6500 (Electronic) IS - 1058-2746 (Print) IS - 1058-2746 (Linking) VI - 24 IP - 3 DP - 2015 Mar TI - Identification of shoulder osteoarthritis biomarkers: comparison between shoulders with and without osteoarthritis. PG - 382-90 LID - S1058-2746(14)00661-2 [pii] LID - 10.1016/j.jse.2014.11.039 [doi] AB - 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). MATERIALS AND 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 alpha (TNF-alpha); aggrecanase 2 (ADAMTS5); and Cx43. RESULTS: In osteoarthritic shoulders, Cx43, Cox-2, versican, collagen type I, ADAMTS5, MMP-3, and TNF-alpha 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-alpha expression being significantly increased. These genes might be useful biomarkers for examining shoulder OA. CLINICAL RELEVANCE: Identification of osteoarthritic biomarkers can help us better understand shoulder OA and build the foundation for future research on disease progression and treatments. CI - Copyright (c) 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved. FAU - Casagrande, Danielle AU - Casagrande D AD - Department of Orthopaedics, University of Maryland, Baltimore, MD, USA. FAU - Stains, Joseph P AU - Stains JP AD - Department of Orthopaedics, University of Maryland, Baltimore, MD, USA. Electronic address: jstains@umoa.umm.edu. FAU - Murthi, Anand M AU - Murthi AM AD - Department of Orthopaedics, University of Maryland, Baltimore, MD, USA. LA - eng GR - R01 AR052719/AR/NIAMS NIH HHS/United States GR - R01 AR063631/AR/NIAMS NIH HHS/United States PT - Journal Article DEP - 20150113 PL - United States TA - J Shoulder Elbow Surg JT - Journal of shoulder and elbow surgery JID - 9206499 RN - 0 (Biomarkers) RN - 0 (Connexin 43) RN - 0 (GJA1 protein, human) RN - 0 (Interleukins) RN - 0 (Tissue Inhibitor of Metalloproteinases) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (VCAN protein, human) RN - 126968-45-4 (Versicans) RN - 9007-34-5 (Collagen) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (PTGS2 protein, human) RN - EC 3.4.24.- (ADAM Proteins) RN - EC 3.4.24.- (ADAMTS5 Protein) RN - EC 3.4.24.- (ADAMTS5 protein, human) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - ADAM Proteins/biosynthesis MH - ADAMTS5 Protein MH - Adult MH - Aged MH - Biomarkers/*metabolism MH - Cartilage, Articular/*chemistry MH - Collagen/biosynthesis MH - Connexin 43/*analysis MH - Cyclooxygenase 2/biosynthesis MH - Female MH - Humans MH - Humeral Head/*chemistry MH - Interleukins/biosynthesis MH - Male MH - Matrix Metalloproteinases/biosynthesis MH - Middle Aged MH - Nitric Oxide Synthase Type II/biosynthesis MH - Osteoarthritis/genetics/*metabolism MH - Shoulder Joint/*chemistry MH - Tissue Inhibitor of Metalloproteinases/biosynthesis MH - Tumor Necrosis Factor-alpha/biosynthesis MH - Up-Regulation MH - Versicans/biosynthesis PMC - PMC4331258 MID - NIHMS655899 OTO - NOTNLM OT - Shoulder OT - biomarkers OT - connexin 43 OT - osteoarthritis EDAT- 2015/01/18 06:00 MHDA- 2015/07/07 06:00 PMCR- 2016/03/01 CRDT- 2015/01/18 06:00 PHST- 2013/12/30 00:00 [received] PHST- 2014/11/12 00:00 [revised] PHST- 2014/11/15 00:00 [accepted] PHST- 2015/01/18 06:00 [entrez] PHST- 2015/01/18 06:00 [pubmed] PHST- 2015/07/07 06:00 [medline] PHST- 2016/03/01 00:00 [pmc-release] AID - S1058-2746(14)00661-2 [pii] AID - 10.1016/j.jse.2014.11.039 [doi] PST - ppublish SO - J Shoulder Elbow Surg. 2015 Mar;24(3):382-90. doi: 10.1016/j.jse.2014.11.039. Epub 2015 Jan 13.