Kamatsuki Yusuke, Aoyama Eriko, Furumatsu Takayuki, Miyazawa Shinichi, Maehara Ami, Yamanaka Nobuyasu, Nishida Takashi, Kubota Satoshi, Ozaki Toshifumi, Takigawa Masaharu
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama, 700-8558, Japan.
Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Dental School/Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan.
J Cell Commun Signal. 2019 Jun;13(2):193-207. doi: 10.1007/s12079-018-0496-9. Epub 2018 Nov 20.
Menisci are a pair of crescent-shaped fibrocartilages, particularly of which their inner region of meniscus is an avascular tissue. It has characteristics similar to those of articular cartilage, and hence is inferior in healing. We previously reported that low-intensity pulsed ultrasound (LIPUS) treatment stimulates the production of CCN2/CTGF, a protein involved in repairing articular cartilage, and the gene expression of major cartilage matrices such as type II collagen and aggrecan in cultured chondrocytes. Therefore, in this present study, we investigated whether LIPUS has also favorable effect on meniscus cells and tissues. LIPUS applied with a 60 mW/cm intensity for 20 min stimulated the gene expression and protein production of CCN2 via ERK and p38 signaling pathways, as well as gene expression of SOX9, aggrecan, and collagen type II in human inner meniscus cells in culture, and slightly stimulated the gene expression of CCN2 and promoted the migration in human outer meniscus cells in culture. LIPUS also induced the expression of Ccn2, Sox9, Col2a1, and Vegf in rat intact meniscus. Furthermore, histological evaluations showed that LIPUS treatment for 1 to 4 weeks promoted healing of rat injured lateral meniscus, as evidenced by better and earlier angiogenesis and extracellular matrix synthesis. The data presented indicate that LIPUS treatment might prevent meniscus from degenerative change and exert a reparative effect on injured meniscus via up-regulation of repairing factors such as CCN2 and that it might thus be useful for treatment of an injured meniscus as a non-invasive therapy.
半月板是一对新月形纤维软骨,其中半月板的内部区域是无血管组织。它具有与关节软骨相似的特性,因此愈合能力较差。我们之前报道过,低强度脉冲超声(LIPUS)治疗可刺激CCN2/结缔组织生长因子的产生,CCN2/结缔组织生长因子是一种参与关节软骨修复的蛋白质,还可刺激培养的软骨细胞中主要软骨基质如II型胶原蛋白和聚集蛋白聚糖的基因表达。因此,在本研究中,我们调查了LIPUS对半月板细胞和组织是否也有有益作用。以60 mW/cm的强度施加LIPUS 20分钟,可通过ERK和p38信号通路刺激培养的人内侧半月板细胞中CCN2的基因表达和蛋白质产生,以及SOX9、聚集蛋白聚糖和II型胶原蛋白的基因表达,并轻微刺激培养的人外侧半月板细胞中CCN2的基因表达并促进其迁移。LIPUS还可诱导大鼠完整半月板中Ccn2、Sox9、Col2a1和Vegf的表达。此外,组织学评估表明,LIPUS治疗1至4周可促进大鼠外侧半月板损伤的愈合,表现为更好、更早的血管生成和细胞外基质合成。所呈现的数据表明,LIPUS治疗可能通过上调CCN2等修复因子来防止半月板退变,并对损伤的半月板发挥修复作用,因此作为一种非侵入性治疗方法,它可能对治疗损伤的半月板有用。