Differential Regulation of Proteoglycan-4 Expression by IL-1.ALPHA. and TGF-.BETA.1 in Rat Condylar Chondrocytes

Abstract

Proteoglycan 4 (PRG4) is a multifaceted glycoprotein that mediates boundary lubrication of articular cartilage and its dysregulation is associated with impaired lubrication and cartilage destruction in multiple synovial joints. However, the spatiotemporal expression of PRG4 and the associated regulatory networks remain largely unknown in the mandibular condylar cartilage that is responsible for homeostasis and functions of the temporomandibular joint. We here investigated the possible regulatory effects of the interleukin-1α (IL-1α ) or/and transforming growth factor-β 1 (TGF-β 1) on the expression of PRG4 in primary chondrocytes that were isolated from the superficial layer of the condylar cartilage of the 20-day-old male Sprague-Dawley rats. Both IL-1α and TGF-β 1 have been implicated in joint destruction and repair. Treatment of primary chondrocytes for 24 h with recombinant human (rh) IL-1α (10 ng/ml) resulted in pronounced reduction in the expression levels of PRG4 mRNA and protein, whereas stimulation with rhTGF-β 1 (10 ng/ml) significantly increased the expression levels, as measured by RT-PCR and ELISA, respectively. Moreover, rhTGF-β 1 was capable to antagonize the inhibitory effects on the PRG4 expression caused by rhIL-1α and robustly restored its abundance in the cultured condylar chondrocytes. Taken together, our data indicate that PRG4 is synthesized and secreted by condylar cartilage chondrocytes and its expression is differentially regulated by IL-1α and TGF-β 1. The rhIL-1α -mediated PRG4 repression is reversible and potently antagonized by rhTGF-β 1 in condylar chondrocytes. The observed up-regulation of PRG4 upon rhTGF-β 1 treatment further supports the therapeutic application of rhTGF-β 1 in the treatment of temporomandibular joint osteoarthritis.

Reduction of friction by recombinant human proteoglycan 4 in IL‐1α stimulated bovine cartilage explants

“…Prior studies indicate that PRG4 protein levels are decreased with inflammation, and that PRG4 mRNA expression is down regulated . However, PRG4 levels were increased at certain time‐points in models of PTOA .…”

“…Overexpression of IL‐1β in rabbits results in cellular hyperplasia, articular cartilage loss, and clinical synovitis . Isolated bovine and rat chondrocytes treated with IL‐1α showed decreased PRG4 secretion and decreased PRG4 expression . IL‐1β has also been shown to down‐regulate PRG4 expression in chondrocytes .…”

“…Isolated bovine and rat chondrocytes treated with IL‐1α showed decreased PRG4 secretion and decreased PRG4 expression . IL‐1β has also been shown to down‐regulate PRG4 expression in chondrocytes . However, other studies suggest that inflammation increases PRG4 production .…”

Synoviocytes protect cartilage from the effects of injury in vitro

“…Transforming growth factor β is an anabolic factor that induces chondrocyte synthesis of ECM molecules by mesenchymal stem cells and chondrocytes [39,40] and leads to increased chondrocyte proliferation [41]. Although the results seem contradictory, it is not uncommon for chondrocytes to express both anabolic and catabolic genes at one time, and may reflect an attempt of chondrocytes at cartilage repair and remodeling.…”

Análise da estrutura e padrão de expressão de lubricina, SMAD2 fosforilada na cadeia de ligação e colágeno tipo I na cartilagem articular da mandíbula durante o envelhecimento

“…A CAM é submetida a forças funcionais, compressivas e friccionais, resultantes dos complexos movimentos mandibulares que incluem rotação e translação [6][7][8] . Assim, para manter a sua integridade, é essencial um baixo coeficiente de atrito obtido, em parte, pela lubrificação das faces articulares.…”