Sprifermin treatment enhances cartilage integration in an in vitro repair model.
Sprifermin treatment enhances cartilage integration in an in vitro repair model.
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DOI：
10.1002/jor.24048
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Dodge GR
中科院分区：
文献类型：
--
作者：
Sennett ML;Meloni GR;Farran AJE;Guehring H;Mauck RL;Dodge GR
软骨整合仍然是治疗局灶性关节缺损的临床挑战。软骨表现出有限的愈合能力，随着组织成熟而下降。已经研究了许多方法来刺激成熟软骨的愈合或修复组织或组织工程结构与天然软骨的整合能力。存在于未成熟组织中的生长因子可能促进软骨形成，促进软骨缺损的综合修复。在这项研究中，我们评估了其中一个因子，成纤维细胞生长因子18 （FGF18）的作用。使用FGF18的研究显示了对软骨的多种积极作用，包括刺激软骨细胞增殖、基质生物合成和抑制蛋白酶活性。为了探索FGF18在软骨缺损修复中的作用，我们假设用重组人FGF18 （sprifermin）处理会增加缺损模型中的基质合成，从而提高整合强度。为了验证这一假设，从幼年牛膝盖上采集了6毫米软骨圆柱体。在每个外植体中形成一个3毫米的中心缺陷，并将该核心移除并更换。结果构建体在对照或含sprifermin的培养基（每周24小时暴露于100 ng/ml sprifermin）中培养4周。采用力学测试、生化分析、显微ct、扫描电镜和组织学来评估基质的生成、粘附强度和软骨-软骨界面的结构特性。结果显示，sprfinmin处理组的黏附强度更大，胶原含量增加，核心和环状软骨之间的接触面积更大。这些发现为软骨损伤提供了一种新的治疗方法，有可能促进缺陷愈合和外侧软骨-软骨融合。
Cartilage integration remains a clinical challenge for treatment of focal articular defects. Cartilage exhibits limited healing capacity that declines with tissue maturation. Many approaches have been investigated for their ability to stimulate healing of mature cartilage or integration of repair tissue or tissue-engineered constructs with native cartilage. Growth factors present in immature tissue may enhance chondrogenesis and promote integrative repair of cartilage defects. In this study, we assessed the role of one such factor, fibroblast growth factor 18 (FGF18). Studies using FGF18 have shown a variety of positive effects on cartilage, including stimulation of chondrocyte proliferation, matrix biosynthesis, and suppression of proteinase activity. To explore the role of FGF18 on cartilage defect repair, we hypothesized that treatment with recombinant human FGF18 (sprifermin) would increase matrix synthesis in a defect model, thus improving integration strength. To test this hypothesis, 6 mm cartilage cylinders were harvested from juvenile bovine knees. A central 3 mm defect was created in each explant, and this core was removed and replaced. Resulting constructs were cultured in control or sprifermin-containing medium (weekly 24-hour exposure of 100 ng/ml sprifermin) for 4 weeks. Mechanical testing, biochemical analysis, micro-CT, scanning electron microscopy, and histology were used to assess matrix production, adhesive strength, and structural properties of the cartilage-cartilage interface. Results showed greater adhesive strength, increased collagen content, and larger contact areas between core and annular cartilage in the sprifermin-treated group. These findings present a novel treatment for cartilage injuries that have potential to enhance defect healing and lateral cartilage-cartilage integration.
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影响因子：
4.6
作者：
Karuppaiah, Kannan;Yu, Kai;Ornitz, David M.
通讯作者：
Ornitz, David M.
影响因子：
4.8
作者：
Niemeyer, Philipp;Porichis, Stella;Salzmann, Gian
通讯作者：
Salzmann, Gian
影响因子：
13.3
作者：
Lohmander, L. Stefan;Hellot, Scarlett;Eckstein, Felix
通讯作者：
Eckstein, Felix
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ
影响因子：
7
作者：
Ellsworth, JL;Berry, J;Hughes, SD
通讯作者：
Hughes, SD