Kojima Yoshitsugu, Watanabe Takayuki
Clinical Pharmacology Research Laboratory, Yokohama University of Pharmacy, 601 Matanocho Totsukaku, Yokohama, Kanagawa, 245-0066, Japan.
Planning and Product Development Division, Nippon Sigmax Co., Ltd., 7th Floor, 1-24-1 Nishi-shinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan.
J Exp Orthop. 2023 Oct 23;10(1):106. doi: 10.1186/s40634-023-00672-2.
Osteoarthritis (OA) is a combination of degeneration and destruction of articular cartilage due to mechanical stress, secondary synovitis, and bone remodelling. In recent years, early knee OA, a preliminary stage of structural failure in OA, has attracted attention as a potential target for therapy to prevent the onset of OA. Intra-articular administration of monoiodoacetic acid (MIA) induces OA-like symptoms, and low doses of MIA induce early OA like symptoms. In this experiment, a low-dose of MIA was induced to early OA model mice, which were then irradiated with low-intensity pulsed ultrasound (LIPUS) to examine whether LIPUS improves symptoms of early OA.
After 4 weeks of LIPUS irradiation, articular cartilage was observed at 1 and 4 weeks. The Osteoarthritis Research Society International (OARSI) scores were calculated using Safranin-O staining results. Cartilage degeneration was detected using Denatured Collagen Detection Reagent (DCDR).
We observed a significant decrease in OARSI scores in the LIPUS irradiated group at week 4. The non-LIPUS group showed widespread areas of double positivity for Type II collagen and DCDR, whereas the LIPUS group showed only a small number of DCDR-positive areas. In addition, macrophage numbers counted in the articular capsule at week 1 showed a significant decrease in the LIPUS irradiated group. Lubricin detection showed that lubricin positive cell number was significantly increased by LIPUS irradiation at week 4.
These results suggest that LIPUS attenuates cartilage degeneration in early OA by relieving inflammation and enhancing the inhibitory effect of lubricin on cartilage degeneration.
骨关节炎（OA）是由于机械应力、继发性滑膜炎和骨重塑导致的关节软骨退变和破坏。近年来，早期膝骨关节炎作为骨关节炎结构破坏的初始阶段，作为预防骨关节炎发病的潜在治疗靶点受到关注。关节内注射单碘乙酸（MIA）可诱发骨关节炎样症状，低剂量MIA可诱发早期骨关节炎样症状。在本实验中，对早期骨关节炎模型小鼠诱导低剂量MIA，然后用低强度脉冲超声（LIPUS）照射，以检查LIPUS是否能改善早期骨关节炎症状。
LIPUS照射4周后，在1周和4周时观察关节软骨。使用番红O染色结果计算国际骨关节炎研究学会（OARSI）评分。使用变性胶原检测试剂（DCDR）检测软骨退变。
我们观察到LIPUS照射组在第4周时OARSI评分显著降低。非LIPUS组显示II型胶原和DCDR双阳性的广泛区域，而LIPUS组仅显示少量DCDR阳性区域。此外，第1周时关节囊中计数的巨噬细胞数量在LIPUS照射组中显著减少。润滑素检测显示，第4周时LIPUS照射显著增加了润滑素阳性细胞数量。
这些结果表明，LIPUS通过减轻炎症和增强润滑素对软骨退变的抑制作用，减轻早期骨关节炎中的软骨退变。
