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      Morphological, Immunocytochemical, and Biochemical Studies of Rat Costal Chondrocytes Exposed to IL-1β and TGF-β1

      Journal of healthcare engineering
      Hindawi Limited

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          Abstract

          This study was undertaken to determine the effects of IL-1 β and TGF- β 1 on the expression of differentiation-associated genes in chondrocytes in vitro. Rat costal chondrocytes were exposed to different concentrations of IL-1 β and TGF- β 1 for 48 h and tested for gene expression. IL-1 β increased the expression of aggrecanase-1 and aggrecanase-2 and decreased the content of aggrecan and collagen II. Low concentration of TGF- β 1 decreased the expression of aggrecan and collagen II and increased the expression of aggrecanase-2. However, the level of aggrecanase-1 was significantly elevated in the presence of high concentration of TGF- β 1. IL-1 β and TGF- β 1 show the ability to modulate the production of aggrecan and collagen II in chondrocytes in vitro.

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          Most cited references32

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          Role of Chondrocytes in Cartilage Formation, Progression of Osteoarthritis and Cartilage Regeneration

          Articular cartilage (AC) covers the diarthrodial joints and is responsible for the mechanical distribution of loads across the joints. The majority of its structure and function is controlled by chondrocytes that regulate Extracellular Matrix (ECM) turnover and maintain tissue homeostasis. Imbalance in their function leads to degenerative diseases like Osteoarthritis (OA). OA is characterized by cartilage degradation, osteophyte formation and stiffening of joints. Cartilage degeneration is a consequence of chondrocyte hypertrophy along with the expression of proteolytic enzymes. Matrix Metalloproteinases (MMPs) and A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) are an example of these enzymes that degrade the ECM. Signaling cascades involved in limb patterning and cartilage repair play a role in OA progression. However, the regulation of these remains to be elucidated. Further the role of stem cells and mature chondrocytes in OA progression is unclear. The progress in cell based therapies that utilize Mesenchymal Stem Cell (MSC) infusion for cartilage repair may lead to new therapeutics in the long term. However, many questions are unanswered such as the efficacy of MSCs usage in therapy. This review focuses on the role of chondrocytes in cartilage formation and the progression of OA. Moreover, it summarizes possible alternative therapeutic approaches using MSC infusion for cartilage restoration.
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            The role of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) in a model of cartilage degradation.

            Cleavage of aggrecan between residues Glu(373)-Ala(374), which is believed to be a key event in aggrecan destruction in arthritic diseases, has been attributed to an enzymatic activity, aggrecanase. Two cartilage aggrecanases have been identified, aggrecanase-1 (ADAM-TS4) and aggrecanase-2 (ADAM-TS5) and both enzymes have been shown very efficiently to cleave soluble aggrecan at the Glu(373)-Ala(374) site. To determine whether ADAM-TS4 and/or ADAM-TS5 are the aggrecanases responsible for aggrecan catabolism following interleukin-1 (IL-1) and tumor necrosis factor (TNF) treatment of bovine articular cartilage. (1) IL-1- and TNF-stimulated release of aggrecan was associated with cleavage of aggrecan within the C-terminus at the ADAM-TS4 and ADAM-TS5-sensitive sites, Glu(1480)-Gly(1481), Glu(1667)-Gly(1668), and Glu(1871)-Leu(1872). (2) The order of cleavage following IL-1 stimulation of cartilage explants was the same as when soluble aggrecan is digested with recombinant human ADAM-TS4 and ADAM-TS5. (3) Both constitutive and stimulated cleavage of aggrecan at the ADAM-TS4 and ADAM-TS5-sensitive sites in cartilage was blocked by a general metalloproteinase inhibitor but not by a MMP-specific inhibitor, and this inhibition correlated with inhibition of aggrecan release from cartilage. (4) PCR and Western blot analysis indicated that both ADAM-TS proteases are expressed in cartilage explants; ADAM-TS5 is constitutively expressed whereas ADAM-TS4 is induced following IL-1 and TNF treatment. (5) Immunodepletion of both ADAM-TS4 and ADAM-TS5 from bovine articular cartilage cultures following IL-1 stimulation resulted in a 90% reduction of aggrecanase activity in the culture medium. Copyright 2001 OsteoArthritis Research Society International.
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              Human Cartilage-Derived Progenitor Cells From Committed Chondrocytes for Efficient Cartilage Repair and Regeneration

              A population of cartilage stem/progenitor cells can be derived from fully differentiated chondrocytes that have the potential to reassume their chondrocytic phenotype for efficient cartilage regeneration. This novel concept supports the possibility of using in vitro amplified chondrocyte-derived progenitor cells for joint repair.
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                Author and article information

                Journal
                10.1155/2017/9747264
                http://creativecommons.org/licenses/by/4.0/

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