Synergistic effect of IGF-1 and OP-1 on matrix formation by normal and OA chondrocytes cultured in alginate beads
Synergistic effect of IGF-1 and OP-1 on matrix formation by normal and OA chondrocytes cultured in alginate beads
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DOI：
10.1016/j.joca.2006.10.004
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发表时间：
2007-04-01
影响因子：
7
通讯作者：
Loeser, R. F.
中科院分区：
文献类型：
--
作者：
Chubinskaya, S.;Hakimiyan, A.;Loeser, R. F.
目的：生长因子疗法可能有助于刺激软骨基质的合成和修复。因此，我们研究的目的是进一步了解胰岛素样生长因子-1 (IGF-1) 和成骨蛋白-1 (OP-1) 联合治疗对成人正常和骨关节炎 (OA) 软骨细胞合成的基质的影响。设计：软骨细胞是在死后从正常人类供体的关节软骨和接受膝关节置换手术的 OA 患者的股骨髁中分离出来的。细胞在藻酸盐珠中培养 21 天，分为四个实验组：（1）“mini-ITS”对照； (2) 100纳克/毫升IGF-1； (3) 100纳克/毫升OP-1； (4) IGF-1 + OP-1，各 100 ng/ml。对珠子进行组织学（番红 O 和固绿）、形态测定和免疫组织化学（聚集蛋白聚糖、核心蛋白聚糖、I、II、VI 和 X 型胶原蛋白以及纤连蛋白积累）分析。结果：组织学显示单独的 IGF-1 不会诱导大量基质产生。 OP-1单独引起大量基质形成，但当OP-1和IGF-1一起添加时，正常软骨细胞和OA软骨细胞的基质积累最高。形态计量分析表明，在联合治疗下，OA 软骨细胞产生的基质比正常细胞产生的基质更大。所有测试的基质蛋白在组合组中都更丰富。 X 型胶原蛋白仅在 OP-1 和 IGF-1 联合治疗下才能检测到，并且含量非常低。 I 型胶原仅在 OA 软骨细胞中发现。结论：当前研究中获得的结果表明，与单独使用任一生长因子相比，IGF-1 和 OP-1 联合治疗在治疗 OA 软骨缺陷方面可能具有更大的潜力。 (C) 2006 年国际骨关节炎研究协会。由爱思唯尔有限公司出版。保留所有权利。
Objective: Growth factor therapy may be useful for stimulation of cartilage matrix synthesis and repair. Thus, the purpose of our study was to further understand the effect of combined insulin-like growth factor-1 (IGF-1) and osteogenic protein-1 (OP-1) treatment on the matrix synthesized by human adult normal and osteoarthritic (OA) chondrocytes.Design: Chondrocytes were isolated post-mortem from articular cartilage from tali of normal human donors and femoral condyles of OA patients undergoing knee replacement surgery. Cells were cultured in alginate beads for 21 days in four experimental groups: (1) "mini-ITS" control; (2) 100 ng/ml IGF-1; (3) 100 ng/ml OP-1; (4) IGF-1 + OP-1, each at 100 ng/ml. Beads were processed for histological (Safranin O and fast green), morphometrical and immunohistochemical (aggrecan, decorin, type I, II, VI, and X collagens, and fibronectin accumulation) analyses.Results: Histology showed that IGF-1 alone did not induce substantial matrix production. OP-1 alone caused a considerable matrix formation, but the highest matrix accumulation by normal and OA chondrocytes was found when OP-1 and IGF-1 were added together. Morphometrical analysis indicated larger matrices produced by OA chondrocytes than by normal cells under the combined treatment. All tested matrix proteins were more abundant in the combination group. Type X collagen was detected only under the combined OP-1 and IGF-1 treatment and was present at very low levels. Type I collagen was found only in OA chondrocytes.Conclusions: The results obtained in the current study suggest that combined therapy with IGF-1 and OP-1 may have a greater potential in treating cartilage defects seen in OA than use of either growth factor alone. (C) 2006 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.