Characterization and Advancement of an Evaluation Method for the Treatment of Spontaneous Osteoarthritis in STR/ort Mice: GRGDS Peptides as a Potential Treatment for Osteoarthritis

Abstract

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.

The role of EDIL3 in maintaining cartilage extracellular matrix and inhibiting osteoarthritis development

“…Illustrative images were obtained using SkyScan DataViewer (version 1.6.0.0; Bruker). These methods were also reported in the study by Chen et al 32 …”

“…Since the male STR/Ort mice develop knee OA spontaneously, as an excellent animal model for OA studies, 57 many studies describe the anatomical and clinical features of the knee joint of STR/ort OA mice as being similar to those of patients with OA; thus, cartilage histological score analyses of STR/ort mice have been confirmed. 32 , 33 Therefore, we carefully examined the Safranin-O-stained image and measured the OARSI score of knee joints in STR/ort mice with or without EDIL3 treatment.…”

“…Past studies have demonstrated that the incidence of degenerative joint disease is higher in male mice than in female mice, and that the medial condyle is much more affected than the lateral condyle. 32 , 33 Therefore, male mice were used in this study.…”