Meniscus is more susceptible than cartilage to catabolic and anti-anabolic effects of adipokines.
Meniscus is more susceptible than cartilage to catabolic and anti-anabolic effects of adipokines.
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DOI：
10.1016/j.joca.2015.04.014
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发表时间：
2015-09
影响因子：
7
通讯作者：
Levenston ME
中科院分区：
文献类型：
--
作者：
Nishimuta JF;Levenston ME
这项研究比较了几种与骨关节炎有关的脂肪因子对软骨和半月板基质分解代谢和生物合成的影响。软骨和半月板外植体在无血清培养液中培养1~9天，或分别加入0.02、0.2或2μg/ml的瘦素、内脂素、脂联素或抵抗素。在培养的最后一天，添加~3H-脯氨酸或35S-硫酸钠来检测蛋白质和硫酸糖胺聚糖(SGAG)的积累。对外植体进行放射标记、SGAG和DNA含量检测。测定培养上清液中SGAG、亚硝酸盐和乳酸脱氢酶活性。软骨组织受脂肪因子的影响最小，与对照组相比，只有最高剂量的抵抗素增加了SGAG的释放和亚硝酸盐的产生。与之形成鲜明对比的是，半月板组织对几种脂肪因子有反应，在抵抗素、瘦素或内脂素治疗后，SGAG和亚硝酸盐释放增加。脂肪因子处理对软骨SGAG含量无明显影响，而半月板SGAG含量随抵抗素剂量的增加而显着降低。脂肪因子对两种组织的蛋白质(~3H)掺入均无影响。在软骨中，SGAG(35S)掺入与脂肪因子处理没有显著差异，但在半月板中，瘦素、内脂素和抵抗素处理可抑制SGAG(35S)的掺入。我们的结果表明，半月板组织比软骨更容易受到脂肪因子刺激的分解代谢的影响。在所测试的脂肪因子中，抵抗素的作用最强，在两种组织中都能诱导SGAG的释放，并在半月板中耗尽SGAG的含量。这些结果表明，肥胖或关节损伤导致的脂肪因子水平升高可能通过生物途径改变膝关节的机械完整性。
This study compared the effects on cartilage and meniscus matrix catabolism and biosynthesis of several adipokines implicated in osteoarthritis. Cartilage and meniscus explants were cultured for 1 or 9 days in serum-free medium alone or with 0.02, 0.2, or 2μg/ml of leptin, visfatin, adiponectin, or resistin. Media were supplemented with 3H-proline or 35S-sodium sulfate to evaluate protein and sulfated glycosaminoglycan (sGAG) accumulation on the last day of culture. Explants were assayed for radiolabel, sGAG, and DNA contents. Cultured media were assayed for sGAG, nitrite and lactate dehydrogenase. Cartilage tissue was minimally affected by adipokines, with only the highest resistin dose increasing sGAG release and nitrite production compared to controls. In sharp contrast, meniscus tissue was responsive to several adipokines, with elevated sGAG and nitrite release following treatment with resistin, leptin, or visfatin. Cartilage sGAG content was unaltered by adipokine treatment whereas meniscal sGAG content significantly decreased with resistin dosage. Protein (3H) incorporation was unaffected by adipokine treatment in both tissues. sGAG (35S) incorporation did not significantly vary with adipokine treatment in cartilage but was inhibited by treatment with leptin, visfatin, and resistin in meniscus. Our results indicate that meniscal tissue is more susceptible to adipokine-stimulated catabolism than is cartilage. Resistin had the strongest effect of the adipokines tested, inducing sGAG release in both tissues and depleting sGAG content in meniscus. These results suggest that increased adipokine levels due to obesity or joint injury may alter the mechanical integrity of the knee joint through biological pathways.