Research Center of TMJ Biology, Institute of Stomatology, Nanjing Medical University, Nanjing, Jiangsu province, China.
Tohoku J Exp Med. 2010 Nov;222(3):211-8. doi: 10.1620/tjem.222.211.
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.
蛋白聚糖 4（PRG4）是一种多功能糖蛋白，可介导关节软骨的边界润滑，其失调与多个滑液关节的润滑功能受损和软骨破坏有关。然而，在负责颞下颌关节的稳态和功能的下颌髁突软骨中，PRG4 的时空表达及其相关调控网络在很大程度上仍不清楚。我们在此研究了白细胞介素-1α（IL-1α）和/或转化生长因子-β1（TGF-β1）对从小鼠 20 日龄髁突软骨浅层分离的原代软骨细胞中 PRG4 表达的可能调控作用。IL-1α 和 TGF-β1 都与关节破坏和修复有关。用重组人（rh）IL-1α（10ng/ml）处理原代软骨细胞 24h 后，PRG4 mRNA 和蛋白的表达水平明显降低，而用 rhTGF-β1（10ng/ml）刺激后，分别通过 RT-PCR 和 ELISA 测量，其表达水平显著增加。此外，rhTGF-β1 能够拮抗 rhIL-1α 对 PRG4 表达的抑制作用，并在培养的髁突软骨细胞中恢复其丰度。总之，我们的数据表明 PRG4 由髁突软骨细胞合成和分泌，其表达受 IL-1α 和 TGF-β1 的差异调控。rhIL-1α 介导的 PRG4 抑制作用是可逆的，并且在髁突软骨细胞中被 rhTGF-β1 强烈拮抗。rhTGF-β1 处理后 PRG4 的上调进一步支持 rhTGF-β1 在治疗颞下颌关节骨关节炎中的治疗应用。
