Nishimuta J F, Levenston M E
Department of Mechanical Engineering, Stanford University, Stanford, CA 94305, USA.
Department of Mechanical Engineering, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Osteoarthritis Cartilage. 2015 Sep;23(9):1551-62. doi: 10.1016/j.joca.2015.04.014. Epub 2015 Apr 23.
This study compared the effects on cartilage and meniscus matrix catabolism and biosynthesis of several adipokines implicated in osteoarthritis (OA).
Bovine cartilage and meniscus explants were cultured for 1 or 9 days in serum-free medium alone or with 0.02, 0.2, or 2 μg/ml of leptin, visfatin, adiponectin, or resistin. Media were supplemented with (3)H-proline or (35)S-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 ((3)H) incorporation was unaffected by adipokine treatment in both tissues. sGAG ((35)S) 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.
本研究比较了几种与骨关节炎（OA）相关的脂肪因子对软骨和半月板基质分解代谢及生物合成的影响。
将牛软骨和半月板外植体在无血清培养基中单独培养1天或9天，或与0.02、0.2或2μg/ml的瘦素、内脂素、脂联素或抵抗素一起培养。在培养基中添加（3）H-脯氨酸或（35）S-硫酸钠，以评估培养最后一天蛋白质和硫酸化糖胺聚糖（sGAG）的积累情况。对外植体进行放射性标记、sGAG和DNA含量检测。对培养基进行sGAG、亚硝酸盐和乳酸脱氢酶检测。
软骨组织受脂肪因子影响最小，与对照组相比，只有最高剂量的抵抗素增加了sGAG释放和亚硝酸盐生成。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，用抵抗素、瘦素或内脂素处理后，sGAG和亚硝酸盐释放增加。脂肪因子处理未改变软骨sGAG含量，而半月板sGAG含量随抵抗素剂量增加而显著降低。两种组织中蛋白质（（3）H）掺入不受脂肪因子处理影响。软骨中sGAG（（35）S）掺入随脂肪因子处理无显著变化，但在半月板中，瘦素、内脂素和抵抗素处理会抑制其掺入。
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，在两种组织中均诱导sGAG释放，并使半月板中sGAG含量减少。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学途径改变膝关节的机械完整性。
