Chen Mei-Feng, Hu Chih-Chien, Hsu Yung-Heng, Chiu Yu-Tien, Chen Kai-Lin, Ueng Steve W N, Chang Yuhan
Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan.
Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan.
Biomedicines. 2023 Apr 6;11(4):1111. doi: 10.3390/biomedicines11041111.
STR/ort mice spontaneously exhibit the typical osteoarthritis (OA) phenotype. However, studies describing the relationship between cartilage histology, epiphyseal trabecular bone, and age are lacking. We aimed to evaluate the typical OA markers and quantify the subchondral bone trabecular parameters in STR/ort male mice at different weeks of age. We then developed an evaluation model for OA treatment. We graded the knee cartilage damage using the Osteoarthritis Research Society International (OARSI) score in STR/ort male mice with or without GRGDS treatment. We measured the levels of typical OA markers, including aggrecan fragments, matrix metallopeptidase-13 (MMP-13), collagen type X alpha 1 chain (COL10A1), and SRY-box transcription factor 9 (Sox9), and quantified epiphyseal trabecular parameters. Compared to the young age group, elderly mice showed an increased OARSI score, decreased chondrocyte columns of the growth plate, elevated expression of OA markers (aggrecan fragments, MMP13, and COL10A1), and decreased expression of Sox9 at the articular cartilage region in elderly STR/ort mice. Aging also significantly enhanced the subchondral bone remodeling and microstructure change in the tibial plateau. Moreover, GRGDS treatment mitigated these subchondral abnormalities. Our study presents suitable evaluation methods to characterize and measure the efficacy of cartilage damage treatments in STR/ort mice with spontaneous OA.
STR/ort小鼠会自发表现出典型的骨关节炎（OA）表型。然而，缺乏描述软骨组织学、骨骺小梁骨与年龄之间关系的研究。我们旨在评估STR/ort雄性小鼠在不同周龄时的典型OA标志物，并量化其软骨下骨小梁参数。然后，我们建立了一种OA治疗评估模型。我们使用国际骨关节炎研究学会（OARSI）评分对接受或未接受GRGDS治疗的STR/ort雄性小鼠的膝关节软骨损伤进行分级。我们测量了典型OA标志物的水平，包括聚集蛋白聚糖片段、基质金属蛋白酶-13（MMP-13）、X型胶原α1链（COL10A1）和SRY盒转录因子9（Sox9），并量化了骨骺小梁参数。与年轻组相比，老年STR/ort小鼠的OARSI评分增加、生长板软骨细胞柱减少、OA标志物（聚集蛋白聚糖片段、MMP13和COL10A1）表达升高、关节软骨区域的Sox9表达降低。衰老还显著增强了胫骨平台软骨下骨重塑和微观结构变化。此外，GRGDS治疗减轻了这些软骨下异常。我们的研究提出了合适的评估方法，以表征和测量自发OA的STR/ort小鼠软骨损伤治疗的疗效。
