Inhibition of integrative cartilage repair by proteoglycan 4 in synovial fluid
Inhibition of integrative cartilage repair by proteoglycan 4 in synovial fluid
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DOI：
10.1002/art.20986
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发表时间：
2005-04-01
影响因子：
--
通讯作者：
Sah, RL
中科院分区：
文献类型：
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作者：
Englert, C;McGowan, KB;Sah, RL
目的探讨关节软骨表面及滑液(SF)及其成分，特别是蛋白多糖4(PRG4)和透明质酸(HA)对体外整体软骨修复的影响。取小牛关节软骨块，一些关节表面完好，另一些则没有。后一种类型的部分块先用胰酶处理，然后用牛血清白蛋白、SF、PRG4或HA处理。治疗结束后在软骨表面进行PRG4免疫定位。将两对相似处理的软骨块在添加血清和~H-Pro的培养液中部分贴合培养2周。培养后，通过测量粘附力来评价软骨块之间的机械结合，并通过掺入~H-脯氨酸来确定蛋白质的生物合成和沉积。关节面对位的标本与切面对位的标本相比，整体性修复较少。PRG4免疫定位于关节软骨表面，但不在更深的切割面(未经治疗)。经胰酶处理后再用SF或PRG4处理的软骨样品，与正常切割的软骨样品相比，其表面的整合修复受到抑制，且PRG4呈阳性免疫染色，而经HA处理的样品在组织表面既没有被抑制的整合修复，也没有PRG4的表达。在整合差异显著的条件下，新合成的蛋白质的沉积相对相似。这些结果支持这样一种观点，即正常情况下有助于软骨润滑的SF中的PRG4可以抑制软骨的综合修复。这具有防止关节软骨相对表面融合的理想效果，但具有抑制整体修复的不良效果。
To determine the effects of the articular cartilage surface, as well as synovial fluid (SF) and its components, specifically proteoglycan 4 (PRG4) and hyaluronic acid (HA), on integrative cartilage repair in vitro.Methods. Blocks of calf articular cartilage were harvested, some with the articular surface intact and others without. Some of the latter types of blocks were pretreated with trypsin, and then with bovine serum albumin, SF, PRG4, or HA. Immunolocalization of PRG4 on cartilage surfaces was performed after treatment. Pairs of similarly treated cartilage blocks were incubated in partial apposition for 2 weeks in medium supplemented with serum and 3 H-proline. Following culture, mechanical integration between apposed cartilage blocks was assessed by measuring adhesive strength, and protein biosynthesis and deposition were determined by incorporated 3 H-proline.Results. Samples with articular surfaces in apposition exhibited little integrative repair compared with samples with cut surfaces in apposition. PRG4 was immunolocalized at the articular cartilage surface, but not in deeper, cut surfaces (without treatment). Cartilage samples treated with trypsin and then with SF or PRG4 exhibited an inhibition of integrative repair and positive immunostaining for PRG4 at treated surfaces compared with normal cut cartilage samples, while samples treated with HA exhibited neither inhibited integrative repair nor PRG4 at the tissue surfaces. Deposition of newly synthesized protein was relatively similar under conditions in which integration differed significantly.Conclusion. These results support the concept that PRG4 in SF, which normally contributes to cartilage lubrication, can inhibit integrative cartilage repair. This has the desirable effect of preventing fusion of apposing surfaces of articulating cartilage, but has the undesirable effect of inhibiting integrative repair.