The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth
The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth
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DOI：
10.1172/jci200522263
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发表时间：
2005-03-01
影响因子：
15.9
通讯作者：
Carpten, JD
中科院分区：
文献类型：
--
作者：
Rhee, DK;Marcelino, J;Carpten, JD
关节的长期完整性取决于其软骨成分的营养和保护软骨表面免受摩擦引起的磨损。润滑素（一种由PRG 4基因编码的分泌性糖蛋白）的功能缺失突变导致人类常染色体隐性遗传疾病-弯曲指关节病-髋内翻-心包炎综合征（CACP）。CACP的一个主要特征是过早的关节失效。为了阐明润滑素保护关节的机制，我们研究了Prg 4 mRNA在小鼠关节发育过程中的表达，并创建了润滑素突变小鼠。Prg 4在关节腔形成后开始在表面软骨细胞和滑膜细胞中表达，并且在出生后这些细胞仍强烈表达。缺乏润滑素的小鼠是可行的和可生育的。在新生儿期，他们的关节表现正常。随着小鼠年龄的增长，我们观察到软骨表面异常的蛋白质沉积和下面的浅区软骨细胞的消失。除了软骨表面变化和随后的软骨退化之外，关节间隙周围滑膜中的内膜细胞变得增生，这进一步促成了关节衰竭。纯化或重组润滑素抑制这些滑膜细胞在体外的生长。肌腱和腱鞘受累存在于踝关节，观察到这些结构的形态学变化和异常钙化。我们的结论是润滑素在关节和肌腱中具有多种功能，包括保护表面和控制滑膜细胞生长。
The long-term integrity of an articulating joint is dependent upon the nourishment of its cartilage component and the protection of the cartilage surface from friction-induced wear. Loss-of-function mutations in lubricin (a secreted glycoprotein encoded by the gene PRG4) cause the human autosomal recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP). A major feature of CACP is precocious joint failure. In order to delineate the mechanism by which lubricin protects joints, we studied the expression of Prg4 mRNA during mouse joint development, and we created lubricin-mutant mice. Prg4 began to be expressed in surface chondrocytes and synoviocytes after joint cavitation had occurred and remained strongly expressed by these cells postnatally. Mice lacking lubricin were viable and fertile. In the newborn period, their joints appeared normal. As the mice aged, we observed abnormal protein deposits on the cartilage surface and disappearance of underlying superficial zone chondrocytes. In addition to cartilage surface changes and subsequent cartilage deterioration, intimal cells in the synovium surrounding the joint space became hyperplastic, which further contributed to joint failure. Purified or recombinant lubricin inhibited the growth of these synoviocytes in vitro. Tendon and tendon sheath involvement was present in the ankle joints, where morphologic changes and abnormal calcification of these structures were observed. We conclude that lubricin has multiple functions in articulating joints and tendons that include the protection of surfaces and the control of synovial cell growth.