Identification of shoulder osteoarthritis biomarkers: comparison between shoulders with and without osteoarthritis

Abstract

Background The biological factors associated with shoulder osteoarthritis (OA) have not been elucidated. The purpose of this study was to investigate putative osteoarthritic biomarkers of the shoulder. To our knowledge, this is the first study to analyze shoulder cartilage for OA-associated genes and examine human shoulder cartilage for a novel biomarker, connexin 43 (Cx43). Materials and methods Cartilage from 16 osteoarthritic and 10 non-osteoarthritic humeral heads was assessed for expression of the following genes via real-time polymerase chain reaction: types I, II, and X collagen, metalloproteinases (MMP), tissue inhibitors of MMP (TIMP), interleukins, versican, cyclooxygenase-2 (Cox-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNFα), aggrecanase-2 (ADAMTS5), and Cx43. Results 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 non-osteoarthritic controls. Spearman correlation analysis showed significant correlations between Cx43 and collagen types I, II, and X, MMP-9, TIMP-2 and -3, versican, Cox-2, iNOS, and ADAMTS5. In osteoarthritic shoulders, Cx43, Cox-2, versican, collagen type I, ADAMTS5, MMP3, and TNFα expressions were significantly increased compared with controls. TIMP-3 and iNOS trended toward significance, with robust expression in osteoarthritic shoulders and low expression in non-osteoarthritic shoulders. Conclusions Certain genes are markedly up-regulated in osteoarthritic shoulders compared with non-osteoarthritic shoulders, with Cx43, Cox-2, versican, collagen type I, ADAMTS5, MMP3, and TNFα expression being significantly increased. These genes might be useful biomarkers for examining shoulder OA.

Correlation between synovial fluid cytokine concentrations and limb function in normal dogs and in dogs with lameness from spontaneous osteoarthritis

“…Particular MMP have been identified in higher concentrations in synovial fluid of osteoarthritic joints compared with normal joints and remain elevated for long periods of time in injured joints, thus having the potential to be reliable indicators of joint environment changes after treatment . In addition, the consistency in elevation has led authors to propose the application of MMP as markers throughout the progression of OA . The increased TIMP concentrations observed in our study are in line with a previous report in which increased TIMP‐3 expression in arthritic joints was attributed to pathological remodeling .…”

Morphological Study: Ultrastructural Aspects of Articular Cartilage and Subchondral Bone in Patients Affected by Post‐Traumatic Shoulder Instability

“…It would be crucial to correlate ultrastructural alterations inside the glenoid articular osteo‐chondral complex, showed for the first time in this article, with the different gene expression observed by many authors in shoulder (Marino et al, ; Mayan et al, ; Casagrande et al, ). In particular, Casagrande et al () showed that certain genes are markedly up‐regulated in osteoarthritic shoulders compared with non‐osteoarthritic ones; in particular, Cx43, Cox‐2, versican, collagen type I, ADAMTS5, MMP‐3, and TNF‐α expression resulted significantly increased. The same authors also suggest that these genes might be useful biomarkers for examining shoulder OA.…”

Connexins and pannexins in the skeleton: gap junctions, hemichannels and more

“…Increased presence of gap junction plaques and Cx43 expression have been found in synovial lining cells obtained from the knee of patients with osteoarthritis [157]. Similarly, Cx43 production is increased in the cartilage of the knee and femoral head [20] and in the shoulders of patients with osteoarthritis, suggesting that the molecule might have a role in the pathogenesis of this disease [158]. Consistent with this, Cx43 levels in osteoarthritic cartilage correlate with the expression of several pro-inflammatory and catabolic factors [158].…”

“…Similarly, Cx43 production is increased in the cartilage of the knee and femoral head [20] and in the shoulders of patients with osteoarthritis, suggesting that the molecule might have a role in the pathogenesis of this disease [158]. Consistent with this, Cx43 levels in osteoarthritic cartilage correlate with the expression of several pro-inflammatory and catabolic factors [158]. In line with this notion, silencing of Cx43 expression protected against inflammation and joint destruction in a model of rheumatoid arthritis in rats [159].…”