Okura Toshiaki, Matsushita Masaki, Mishima Kenichi, Esaki Ryusaku, Seki Taisuke, Ishiguro Naoki, Kitoh Hiroshi
Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-8550, Japan.
J Orthop Res. 2018 Jan;36(1):300-308. doi: 10.1002/jor.23608. Epub 2017 Jun 6.
The purpose of this study is to investigate the morphometric changes of the subchondral bone during the development of osteoarthritis (OA) in transgenic mice with achondroplasia (Fgfr3 ) carrying a heterozygous gain-of-function mutation in Fgfr3. Two OA models (spontaneously developed with age: The aging model, and surgically induced by destabilization of the medial meniscus: The DMM model) were established. Articular cartilage, epiphysis, and metaphysis of the knee joint were histologically and morphometrically compared between wild-type mice, and Fgfr3 mice in both OA models. Articular cartilage degeneration was scored according to the Osteoarthritis Research Society International (OARSI) scoring system. Several morphometric parameters including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular bone thickness (Tb.Th), and subchondral bone thickness in the medial tibial plateau (MTP) (Sb.Th med) were quantified by micro-computed tomography (CT). In the aging model, although there were no significant differences in the OARSI score between wild-type mice and Fgfr3 mice, Sb.Th med and Tb.Th in the epiphysis significantly increased in wild-type mice. In the DMM model, the OARSI score of the medial compartment was significantly lower in Fgfr3 mice than in wild-type mice. BMD, BV/TV, and Tb.Th in the epiphysis increased in wild-type mice and unchanged in Fgfr3 mice, and the Sb.Th med was significantly larger in wild-type mice after surgery. Subchondral sclerosis, which preceded the cartilage degeneration, was inhibited in Fgfr3 mice. Activated FGFR3 signaling prevented sclerotic changes of the subchondral bone and subsequent cartilage degeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:300-308, 2018.
本研究旨在调查携带成纤维细胞生长因子受体3（Fgfr3）功能获得性杂合突变的软骨发育不全转基因小鼠（Fgfr3）骨关节炎（OA）发展过程中软骨下骨的形态计量学变化。建立了两种OA模型（随年龄自发形成：衰老模型，以及通过内侧半月板失稳手术诱导：DMM模型）。对野生型小鼠与两种OA模型中的Fgfr3小鼠的膝关节软骨、骨骺和干骺端进行了组织学和形态计量学比较。根据国际骨关节炎研究学会（OARSI）评分系统对关节软骨退变进行评分。通过微型计算机断层扫描（CT）对包括骨密度（BMD）、骨体积/组织体积（BV/TV）、小梁骨厚度（Tb.Th）以及胫骨内侧平台（MTP）的软骨下骨厚度（Sb.Th med）等几个形态计量学参数进行量化。在衰老模型中，尽管野生型小鼠与Fgfr3小鼠的OARSI评分无显著差异，但野生型小鼠骨骺处的Sb.Th med和Tb.Th显著增加。在DMM模型中，Fgfr3小鼠内侧间室的OARSI评分显著低于野生型小鼠。野生型小鼠骨骺处的BMD、BV/TV和Tb.Th增加，而Fgfr3小鼠无变化，且手术后野生型小鼠的Sb.Th med显著更大。在Fgfr3小鼠中，软骨退变之前的软骨下硬化受到抑制。激活的FGFR3信号传导可防止软骨下骨的硬化改变及随后的软骨退变。©2017骨科学研究学会。由威利期刊公司出版。《矫形外科学研究》36:300 - 308，2018年。
