Cartilage boundary lubricating ability of aldehyde modified proteoglycan 4 (PRG4-CHO).
Cartilage boundary lubricating ability of aldehyde modified proteoglycan 4 (PRG4-CHO).
复制标题
醛修饰蛋白聚糖4（PRG4-CHO）的软骨边界润滑能力。
DOI：
10.1016/j.joca.2012.09.016
复制
发表时间：
2013
影响因子：
7
通讯作者：
Schmidt,TA
中科院分区：
文献类型：
--
作者：
Abubacker,S;Ham,HO;Messersmith,PB;Schmidt,TA
蛋白聚糖4（PRG 4），也称为润滑素1和浅区蛋白2，是一种粘液糖蛋白，存在于滑液（SF）和关节软骨表面，在那里它作为关节健康所需的关键边界润滑剂3。高摩擦和高磨损是可能导致软骨退化的许多因素之一4。PRG 4在减少摩擦和最小化软骨表面的表面组织剪切5方面至关重要，从而通过边界润滑防止软骨退化。实际上，PRG 4敲除小鼠中增加的摩擦系数与关节面6的磨损增加相关。此外，关节内注射PRG 4已被证明可以防止骨关节炎（OA）损伤后大鼠模型中的软骨退化7。最近的一项研究，以SF中PRG 4水平降低与早期OA相关为动机，证明PRG 4的醛修饰（PRG 4-CHO）显著增强了其与耗尽关节面的结合8。这种修饰可能有助于通过增加在关节内的停留时间和/或结合到关节软骨表面来改善PRG 4对早期OA的生物相容性治疗。然而，PRG 4-CHO是否保持未修饰的PRG 4的减摩能力仍有待确定。因此，本研究的目的是使用先前描述的体外软骨-软骨摩擦测试5、9评估PRG 4-CHO相对于未修饰的PRG 4的软骨边界润滑能力。本研究的结果表明，醛修饰不会显著影响PRG 4的蛋白质结构或润滑功能，PRG 4-CHO是一种有效的摩擦减少软骨边界润滑剂。这些结果连同先前发表的数据8共同表明PRG 4-CHO可用于需要润滑的组织表面的分子表面重建策略，以及潜在的其他生物界面或生物材料。
Proteoglycan 4 (PRG4), also known as lubricin 1 and superficial zone protein 2, is a mucinous glycoprotein that is present in synovial fluid (SF) and at the surface of articular cartilage, where it functions as a critical boundary lubricant necessary for joint health 3. High friction and high wear are amongst many factors that may contribute to cartilage degeneration 4. PRG4 is critical in reducing friction and minimising surface tissue shear 5 at the surface of cartilage, thus preventing the degradation of cartilage through boundary lubrication. Indeed, an increased coefficient of friction in PRG4-knockout mice is associated with increased wear of the articular surface 6. Furthermore, intra-articular injection of PRG4 has been shown to prevent cartilage degradation in post-injury rat models of osteoarthritis (OA) 7. A recent study, motivated by diminished PRG4 levels in SF associated with early OA, demonstrated aldehyde modification of PRG4 (PRG4-CHO) significantly enhanced its binding to a depleted articular surface 8. Such modification may contribute to an improved biotherapeutic treatment of early OA with PRG4 through enhanced residence time within the joint and/or binding to the articular cartilage surface. However, it remains to be determined if PRG4-CHO maintains the friction-reducing ability of unmodified PRG4. Therefore, the objective of this study was to assess the cartilage boundary lubricating ability of PRG4-CHO vs unmodified PRG4 using a previously described in vitro cartilage–cartilage friction test 5, 9. The findings of this study indicate that aldehyde modification does not significantly affect the protein structure or lubricating function of PRG4, and PRG4-CHO is an effective friction reducing cartilage boundary lubricant. These results, together with previously published data 8, collectively suggest PRG4-CHO may be useful in molecular resurfacing strategies for tissue surfaces requiring lubrication, and potentially other biointerfaces or biomaterials as well.