Ozeki Nobutake, Muneta Takeshi, Koga Hideyuki, Katagiri Hiroki, Otabe Koji, Okuno Makiko, Tsuji Kunikazu, Kobayashi Eiji, Matsumoto Kenji, Saito Hirohisa, Saito Tomoyuki, Sekiya Ichiro
Tokyo Medical and Dental University, Tokyo, Japan; Yokohama City University, Yokohama, Japan.
Arthritis Rheum. 2013 Nov;65(11):2876-86. doi: 10.1002/art.38099.
This study was undertaken to examine whether bone morphogenetic protein 7 (BMP-7) induces ectopic cartilage formation in the rat tendon, and whether transplantation of tendon treated with BMP-7 promotes meniscal regeneration. Additionally, we analyzed the relative contributions of host and donor cells on the healing process after tendon transplantation in a rat model.
BMP-7 was injected in situ into the Achilles tendon of rats, and the histologic findings and gene profile were evaluated. Achilles tendon injected with 1 μg of BMP-7 was transplanted into a meniscal defect in rats. The regenerated meniscus and articular cartilage were evaluated at 4, 8, and 12 weeks. Achilles tendon from LacZ-transgenic rats was transplanted into the meniscal defect in wild-type rats, and vice versa.
Injection of BMP-7 into the rat Achilles tendon induced the fibrochondrocyte differentiation of tendon cells and changed the collagen gene profile of tendon tissue to more closely approximate meniscal tissue. Transplantation of the rat Achilles tendon into a meniscal defect increased meniscal size. The rats that received the tendon treated with BMP-7 had a meniscus matrix that exhibited increased Safranin O and type II collagen staining, and showed a delay in articular cartilage degradation. Using LacZ-transgenic rats, we determined that the regeneration of the meniscus resulted from contribution from both donor and host cells.
Our findings indicate that BMP-7 induces ectopic cartilage formation in rat tendons. Transplantation of Achilles tendon treated with BMP-7 promotes meniscus regeneration and prevents cartilage degeneration in a rat model of massive meniscal defect. Native cells in the rat Achilles tendon contribute to meniscal regeneration.
本研究旨在探讨骨形态发生蛋白7（BMP - 7）是否能诱导大鼠肌腱异位软骨形成，以及用BMP - 7处理的肌腱移植是否能促进半月板再生。此外，我们分析了大鼠模型中肌腱移植后宿主细胞和供体细胞对愈合过程的相对贡献。
将BMP - 7原位注射到大鼠跟腱中，并评估组织学结果和基因谱。将注射1μg BMP - 7的跟腱移植到大鼠半月板缺损处。在4周、8周和12周时评估再生的半月板和关节软骨。将来自LacZ转基因大鼠的跟腱移植到野生型大鼠的半月板缺损处，反之亦然。
向大鼠跟腱注射BMP - 7可诱导肌腱细胞向纤维软骨细胞分化，并使肌腱组织的胶原基因谱更接近半月板组织。将大鼠跟腱移植到半月板缺损处可增加半月板大小。接受用BMP - 7处理的肌腱的大鼠，其半月板基质中番红O和II型胶原染色增加，并且关节软骨退变延迟。利用LacZ转基因大鼠，我们确定半月板的再生来自供体细胞和宿主细胞的共同作用。
我们的研究结果表明，BMP - 7可诱导大鼠肌腱异位软骨形成。在大鼠巨大半月板缺损模型中，用BMP - 7处理的跟腱移植可促进半月板再生并防止软骨退变。大鼠跟腱中的天然细胞有助于半月板再生。
