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-β1 (TGF-β1) 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-β1 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-β1 (10 ng/ml) significantly increased the expression levels, as measured by RT-PCR and ELISA, respectively. Moreover, rhTGF-β1 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-β1. The rhIL-1α-mediated PRG4 repression is reversible and potently antagonized by rhTGF-β1 in condylar chondrocytes. The observed up-regulation of PRG4 upon rhTGF-β1 treatment further supports the therapeutic application of rhTGF-β1 in the treatment of temporomandibular joint osteoarthritis.