Danielle Casagrande1, Joseph P Stains2, Anand M Murthi1. 1. Department of Orthopaedics, University of Maryland, Baltimore, MD, USA. 2. Department of Orthopaedics, University of Maryland, Baltimore, MD, USA. Electronic address: jstains@umoa.umm.edu.
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). 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 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. 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.
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 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. 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.
Authors: S Su; J Grover; P J Roughley; J A DiBattista; J Martel-Pelletier; J P Pelletier; M Zafarullah Journal: Rheumatol Int Date: 1999 Impact factor: 2.631
Authors: Masahiko Kobayashi; Ginette R Squires; Aisha Mousa; Michael Tanzer; David J Zukor; John Antoniou; Ulrich Feige; A Robin Poole Journal: Arthritis Rheum Date: 2005-01
Authors: Joost Willebrords; Sara Crespo Yanguas; Michaël Maes; Elke Decrock; Nan Wang; Luc Leybaert; Brenda R Kwak; Colin R Green; Bruno Cogliati; Mathieu Vinken Journal: Crit Rev Biochem Mol Biol Date: 2016-07-07 Impact factor: 8.250
Authors: Loganathan Rangasamy; Bruno Di Geronimo; Irene Ortín; Claire Coderch; José María Zapico; Ana Ramos; Beatriz de Pascual-Teresa Journal: Molecules Date: 2019-08-16 Impact factor: 4.411
Authors: N Crowe; T E Swingler; L T T Le; M J Barter; G Wheeler; H Pais; S T Donell; D A Young; T Dalmay; I M Clark Journal: Osteoarthritis Cartilage Date: 2015-10-20 Impact factor: 6.576
Authors: Nevzat Selim Gokay; Ibrahim Yilmaz; Baran Komur; Ahu Senem Demiroz; Alper Gokce; Sergülen Dervisoglu; Banu Vural Gokay Journal: Biomed Res Int Date: 2016-06-13 Impact factor: 3.411
Authors: Marta Varela-Eirín; Paula Carpintero-Fernández; Agustín Sánchez-Temprano; Adrián Varela-Vázquez; Carlos Luis Paíno; Antonio Casado-Díaz; Alfonso Calañas-Continente; Virginia Mato; Eduardo Fonseca; Mustapha Kandouz; Alfonso Blanco; José Ramón Caeiro; María D Mayán Journal: Aging (Albany NY) Date: 2020-08-03 Impact factor: 5.955