Davis Sarah, Zekonyte Jurgita, Karali Aikaterina, Roldo Marta, Blunn Gordon
School of Pharmacy and Biomedical Science, University of Portsmouth, Portsmouth PO1 2DT, UK.
School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth PO1 3DJ, UK.
Bioengineering (Basel). 2023 Aug 23;10(9):995. doi: 10.3390/bioengineering10090995.
Understanding early mechanical changes in articular cartilage (AC) and subchondral bone (SB) is crucial for improved treatment of osteoarthritis (OA). The aim of this study was to develop a method for nanoindentation of fresh, unfixed osteochondral tissue to assess the early changes in the mechanical properties of AC and SB. Nanoindentation was performed throughout the depth of AC and SB in the proximal tibia of Dunkin Hartley guinea pigs at 2 months, 3 months, and 2 years of age. The contralateral tibias were either histologically graded for OA or analyzed using immunohistochemistry. The results showed an increase in the reduced modulus (E) in the deep zone of AC during early-stage OA (6.0 ± 1.75 MPa) compared to values at 2 months (4.04 ± 1.25 MPa) (*** < 0.001). In severe OA (2-year) specimens, there was a significant reduction in E throughout the superficial and middle AC zones, which correlated to increased ADAMTS 4 and 5 staining, and proteoglycan loss in these regions. In the subchondral bone, a 35.0% reduction in stiffness was observed between 2-month and 3-month specimens (*** < 0.001). The severe OA age group had significantly increased SB stiffness of 36.2% and 109.6% compared to 2-month and 3-month-old specimens respectively (*** < 0.001). In conclusion, this study provides useful information about the changes in the mechanical properties of both AC and SB during both early- and late-stage OA and indicates that an initial reduction in stiffness of the SB and an increase in stiffness in the deep zone of AC may precede early-stage cartilage degeneration.
了解关节软骨（AC）和软骨下骨（SB）的早期力学变化对于改善骨关节炎（OA）的治疗至关重要。本研究的目的是开发一种用于新鲜、未固定的骨软骨组织纳米压痕的方法，以评估AC和SB力学性能的早期变化。在2个月、3个月和2岁的Dunkin Hartley豚鼠胫骨近端，对AC和SB的整个深度进行纳米压痕测试。对侧胫骨要么进行OA组织学分级，要么使用免疫组织化学进行分析。结果显示，与2个月时的值（4.04±1.25 MPa）相比，早期OA期间AC深层区域的折合模量（E）增加（6.0±1.75 MPa）（***P<0.001）。在严重OA（2年）标本中，整个AC浅层和中层区域的E显著降低，这与这些区域中ADAMTS 4和5染色增加以及蛋白聚糖损失相关。在软骨下骨中，2个月和3个月标本之间观察到刚度降低35.0%（***P<0.001）。与2个月和3个月大的标本相比，严重OA年龄组的SB刚度分别显著增加36.2%和109.6%（***P<0.001）。总之，本研究提供了关于早期和晚期OA期间AC和SB力学性能变化的有用信息，并表明SB刚度的初始降低和AC深层区域刚度的增加可能先于早期软骨退变。
