Lubricin protects the temporomandibular joint surfaces from degeneration.
Lubricin protects the temporomandibular joint surfaces from degeneration.
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DOI：
10.1371/journal.pone.0106497
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Purcell P
中科院分区：
文献类型：
--
作者：
Hill A;Duran J;Purcell P
颞下颌关节 (TMJ) 是一种特殊的滑膜关节，对于哺乳动物下巴的活动和功能至关重要。颞下颌关节由下颌骨髁、颞骨关节窝以及介于这些骨头之间的纤维软骨盘组成。纤维囊通过滑膜排列在管腔表面上，连接这些骨头并将滑液保留在腔内。滑液的主要成分是润滑素，这是一种由蛋白聚糖 4 (Prg4) 基因编码的糖蛋白，由关节软骨表面的软骨细胞和滑膜衬里细胞合成。我们之前表明，在膝关节中，Prg4 对于维持软骨表面和调节滑膜内膜细胞的增殖至关重要。因此，本研究的目的是确定润滑素在维持颞下颌关节中的作用。我们发现缺乏润滑素的小鼠在出生时颞下颌关节正常，但在两个月后会出现类似于颞下颌关节骨关节炎的退化，并且随着时间的推移，其严重程度会增加。 Prg4-/-小鼠的疾病进展导致滑膜增生，髁突、椎间盘和窝软骨退化，软骨细胞数量增加，并重新分布在簇中，并伴有浅层软骨细胞的损失。关节的所有关节表面都有明显的蛋白质沉积层。与膝关节相比，骨关节炎样表型在颞下颌关节中更为严重且表现更早。总而言之，颞下颌关节中缺乏润滑素会导致骨关节炎样变性，影响关节软骨以及多个关节组织的完整性。我们的结果提供了润滑素在 TMJ 中作用的第一个分子证据，并表明 Prg4 −/− 小鼠可能为研究 TMJ 骨关节炎的早期事件提供有价值的新动物模型。
The temporomandibular joint (TMJ) is a specialized synovial joint essential for the mobility and function of the mammalian jaw. The TMJ is composed of the mandibular condyle, the glenoid fossa of the temporal bone, and a fibrocartilagenous disc interposed between these bones. A fibrous capsule, lined on the luminal surface by the synovial membrane, links these bones and retains synovial fluid within the cavity. The major component of synovial fluid is lubricin, a glycoprotein encoded by the gene proteoglycan 4 (Prg4), which is synthesized by chondrocytes at the surface of the articular cartilage and by synovial lining cells. We previously showed that in the knee joint, Prg4 is crucial for maintenance of cartilage surfaces and for regulating proliferation of the intimal cells in the synovium. Consequently, the objective of this study was to determine the role of lubricin in the maintenance of the TMJ. We found that mice lacking lubricin have a normal TMJ at birth, but develop degeneration resembling TMJ osteoarthritis by 2 months, increasing in severity over time. Disease progression in Prg4 −/− mice results in synovial hyperplasia, deterioration of cartilage in the condyle, disc and fossa with an increase in chondrocyte number and their redistribution in clusters with loss of superficial zone chondrocytes. All articular surfaces of the joint had a prominent layer of protein deposition. Compared to the knee joint, the osteoarthritis-like phenotype was more severe and manifested earlier in the TMJ. Taken together, the lack of lubricin in the TMJ causes osteoarthritis-like degeneration that affects the articular cartilage as well as the integrity of multiple joint tissues. Our results provide the first molecular evidence of the role of lubricin in the TMJ and suggest that Prg4 −/− mice might provide a valuable new animal model for the study of the early events of TMJ osteoarthritis.
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