School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, United Kingdom.
Centre for Stress and Age-Related Disease, University of Brighton, Brighton, United Kingdom.
Front Endocrinol (Lausanne). 2021 Oct 20;12:734988. doi: 10.3389/fendo.2021.734988. eCollection 2021.
The purpose of this study was to investigate growth plate dynamics in surgical and loading murine models of osteoarthritis, to understand whether abnormalities in these dynamics are associated with osteoarthritis development. 8-week-old C57BL/6 male mice underwent destabilisation of medial meniscus (DMM) ( 8) surgery in right knee joints. Contralateral left knee joints had no intervention (controls). In 16-week-old C57BL/6 male mice ( = 6), osteoarthritis was induced using non-invasive mechanical loading of right knee joints with peak force of 11N. Non-loaded left knee joints were internal controls. Chondrocyte transiency in tibial articular cartilage and growth plate was confirmed by histology and immunohistochemistry. Tibial subchondral bone parameters were measured using microCT and correlated to 3-dimensional (3D) growth plate bridging analysis. Higher expression of chondrocyte hypertrophy markers; Col10a1 and MMP13 were observed in tibial articular cartilage chondrocytes of DMM and loaded mice. In tibial growth plate, Col10a1 and MMP13 expressions were widely expressed in a significantly enlarged zone of proliferative and hypertrophic chondrocytes in DMM (=0.002 and <0.0001, respectively) and loaded (both <0.0001) tibiae of mice compared to their controls. 3D quantification revealed enriched growth plate bridging and higher bridge densities in medial compared to lateral tibiae of DMM and loaded knee joints of the mice. Growth plate dynamics were associated with increased subchondral bone volume fraction (BV/TV; %) in medial tibiae of DMM and loaded knee joints and epiphyseal trabecular bone volume fraction in medial tibiae of loaded knee joints. The results confirm articular cartilage chondrocyte transiency in a surgical and loaded murine models of osteoarthritis. Herein, we reveal spatial variation of growth plate bridging in surgical and loaded osteoarthritis models and how these may contribute to anatomical variation in vulnerability of osteoarthritis development.
本研究旨在探讨手术和负荷两种骨关节炎小鼠模型中生长板的动力学变化，以了解这些动力学变化是否与骨关节炎的发展有关。8 周龄 C57BL/6 雄性小鼠右膝关节行内侧半月板不稳定（DMM）（8）手术。对侧左膝关节不进行干预（对照组）。在 16 周龄 C57BL/6 雄性小鼠（n=6）中，使用右膝关节非侵入性机械负荷，峰值力为 11N，诱导骨关节炎。未加载的左膝关节作为内部对照。通过组织学和免疫组织化学证实胫骨关节软骨和生长板中的软骨细胞瞬变。使用 microCT 测量胫骨软骨下骨参数，并与 3 维（3D）生长板桥接分析相关联。DMM 和负荷小鼠的胫骨关节软骨软骨细胞中观察到较高的软骨细胞肥大标志物 Col10a1 和 MMP13 的表达。在胫骨生长板中，Col10a1 和 MMP13 的表达在 DMM（分别为 0.002 和 <0.0001）和负荷（均 <0.0001）小鼠的增殖和肥大软骨细胞的显著扩大区域中广泛表达与对照相比。3D 定量显示 DMM 和负荷膝关节的内侧胫骨比外侧胫骨有更多的生长板桥接和更高的桥接密度。生长板动力学与 DMM 和负荷膝关节内侧胫骨的软骨下骨体积分数（BV/TV；%）增加以及负荷膝关节内侧胫骨的骺板小梁骨体积分数增加有关。结果证实了手术和负荷两种骨关节炎小鼠模型中的关节软骨细胞瞬变。在此，我们揭示了手术和负荷骨关节炎模型中生长板桥接的空间变异性，以及这些变异性如何导致骨关节炎发展的解剖变异性。
