Tsukuda Yukinori, Onodera Tomohiro, Ito Masayuki, Izumisawa Yasuharu, Kasahara Yasuhiko, Igarashi Tatsuya, Ohzawa Nobuo, Todoh Masahiro, Tadano Shigeru, Iwasaki Norimasa
Department of Orthopaedic Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
Department of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
J Biomed Mater Res A. 2015 Nov;103(11):3441-8. doi: 10.1002/jbm.a.35490. Epub 2015 May 6.
This study aimed to elucidate the therapeutic effects of intra-articular administration of ultra-purified low endotoxin alginate (UPLE-alginate) on osteoarthritis (OA) using a canine anterior cruciate ligament transection (ACLT) model.
We used 20 beagle dogs. ACLT was performed on the left knee of each dog and a sham operation was performed on the right knee as a control. All animals were randomly divided into the control (saline) and therapeutic (UPLE-alginate) groups. Animals in the control and therapeutic groups received weekly injections with 0.7 mL normal saline or 0.7 mL 0.5% UPLE-alginate, respectively, from 0 to 3 weeks after ACLT or sham operation. At 9 weeks after ACLT, the knee joints of all animals were observed using arthroscopy. All animals were euthanized at 14 weeks after ACLT and evaluated using morphologic assessment, histologic assessment, and biomechanical testing.
Arthroscopic findings showed intact cartilage surface in both groups. Morphologic findings in the therapeutic group showed milder degeneration compared with those of the control group, but there were no significant differences between groups. Histologic scores of the medial femoral condyle (MFC) and lateral femoral condyle (LFC) were better in the therapeutic group than the control group (MFC: p = 0.009, LFC: p = 0.009). Joint lubrication did not differ significantly between groups.
Intra-articular administration of UPLE-alginate in the early stage of OA slowed disease progression in canines. UPLE-alginate may have potential as a therapeutic agent for OA patients and reduce the number of patients who need to undergo total joint arthroplasty.
本研究旨在利用犬前交叉韧带切断术（ACLT）模型阐明关节内注射超纯低内毒素海藻酸盐（UPLE-海藻酸盐）对骨关节炎（OA）的治疗效果。
我们使用了20只比格犬。对每只犬的左膝进行ACLT，并对右膝进行假手术作为对照。所有动物随机分为对照组（生理盐水）和治疗组（UPLE-海藻酸盐）。在ACLT或假手术后0至3周，对照组和治疗组的动物分别每周注射0.7 mL生理盐水或0.7 mL 0.5%的UPLE-海藻酸盐。ACLT后9周，使用关节镜观察所有动物的膝关节。在ACLT后14周对所有动物实施安乐死，并通过形态学评估、组织学评估和生物力学测试进行评价。
关节镜检查结果显示两组软骨表面均完整。治疗组的形态学结果显示与对照组相比退变较轻，但两组之间无显著差异。治疗组股骨内侧髁（MFC）和股骨外侧髁（LFC）的组织学评分优于对照组（MFC：p = 0.009，LFC：p = 0.009）。两组之间的关节润滑情况无显著差异。
OA早期关节内注射UPLE-海藻酸盐可减缓犬类疾病进展。UPLE-海藻酸盐可能有潜力成为OA患者的治疗药物，并减少需要进行全关节置换术的患者数量。
