Human Articular Chondrocytes Express Multiple Gap Junction Proteins

Osteoarthritis (OA) is the most common joint disease and involves progressive degeneration of articular cartilage. The aim of this study was to investigate if chondrocytes from human articular cartilage express gap junction proteins called connexins (Cxs). We show that human chondrocytes in tissue express Cx43, Cx45, Cx32, and Cx46. We also find that primary chondrocytes from adults retain the capacity to form functional voltage-dependent gap junctions. Immunohistochemistry experiments in cartilage from OA patients revealed significantly elevated levels of Cx43 and Cx45 in the superficial zone and down through the next approximately 1000 μm of tissue. These zones corresponded with regions damaged in OA that also had high levels of proliferative cell nuclear antigen. An increased number of Cxs may help explain the increased proliferation of cells in clusters that finally lead to tissue homeostasis loss. Conversely, high levels of Cxs in OA cartilage reflect the increased number of adjacent cells in clusters that are able to interact directly by gap junctions as compared with hemichannels on single cells in normal cartilage. Our data provide strong evidence that OA patients have a loss of the usual ordered distribution of Cxs in the damaged zones and that the reductions in Cx43 levels are accompanied by the loss of correct Cx localization in the nondamaged areas. Osteoarthritis (OA) is the most common joint disease and involves progressive degeneration of articular cartilage. The aim of this study was to investigate if chondrocytes from human articular cartilage express gap junction proteins called connexins (Cxs). We show that human chondrocytes in tissue express Cx43, Cx45, Cx32, and Cx46. We also find that primary chondrocytes from adults retain the capacity to form functional voltage-dependent gap junctions. Immunohistochemistry experiments in cartilage from OA patients revealed significantly elevated levels of Cx43 and Cx45 in the superficial zone and down through the next approximately 1000 μm of tissue. These zones corresponded with regions damaged in OA that also had high levels of proliferative cell nuclear antigen. An increased number of Cxs may help explain the increased proliferation of cells in clusters that finally lead to tissue homeostasis loss. Conversely, high levels of Cxs in OA cartilage reflect the increased number of adjacent cells in clusters that are able to interact directly by gap junctions as compared with hemichannels on single cells in normal cartilage. Our data provide strong evidence that OA patients have a loss of the usual ordered distribution of Cxs in the damaged zones and that the reductions in Cx43 levels are accompanied by the loss of correct Cx localization in the nondamaged areas. The surfaces of articulating bones are covered by articular cartilage, which is required for the smooth and painless movement of the skeleton. Osteoarthritis (OA) is a condition that is characterized by the progressive degradation of matrix components that leads to a loss of joint mobility and function accompanied by chronic pain. OA is the most common joint disorder in Western populations, and its incidence increases with age. The molecular mechanisms regulating the pathogenesis and progression of OA, however, are poorly understood, and no proven disease-modifying therapy is currently available. In adult cartilage, the chondrocytes remain resting in a nonproliferating state, but display moderate metabolic activity and the ability to maintain the surrounding matrix. 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GJs are membrane channels that often assemble as large membrane rafts and are identified as plaques at the membrane surface. Vertebrate GJ channels are composed of proteins encoded by the connexin (Cx) gene family and consist of intercellular channels that directly connect the cytoplasm of adjacent cells.7Sohl G. Willecke K. Gap junctions and the connexin protein family.Cardiovasc Res. 2004; 62: 228-232Crossref PubMed Scopus (788) Google Scholar In addition to their role in providing a pathway for direct intercellular communication, he