Chondrocytes, the resident cells in articular cartilage, carry the burden of producing and maintaining the extracellular matrix (ECM). However, as these cells have a low proliferative capacity and are not readily replaced, chondrocyte death due to extreme forces may contribute to the pathogenesis of osteoarthritis (OA) after injury or may inhibit healing after osteochondral transplantation, a restorative procedure for damaged cartilage that requires a series of mechanical impacts to insert the graft. Consequently, there is a need to understand what factors influence the vulnerability of in situ chondrocytes to mechanical trauma. To this end, the objective of this study was to investigate how altering cell volume by different means (hydrostatic pressure, uniaxial load, and osmotic challenge with and without inhibition of regulatory volume decrease) affects the vulnerability of in situ chondrocytes to extreme mechanical forces. Using a custom experimental platform enabling testing of viable and intact murine cartilage-on-bone explants, we established a strong correlation between chondrocyte volume and vulnerability to impact injury wherein reduced volume was protective. Moreover, we found that the volume-perturbing interventions did not affect cartilage ECM mechanical properties, suggesting that their effects on chondrocyte vulnerability occurred at the cellular level. The findings of this study offer new avenues for novel strategies aimed at preventing chondrocyte loss during osteochondral grafting or to halting the progression of cell death after a joint destabilizing injury.

软骨细胞是关节软骨中的常驻细胞，担负着产生和维持细胞外基质（ECM）的重任。但是，由于这些细胞的增殖能力低且不易被替换，因此，由于极强的力而导致的软骨细胞死亡可能会导致受伤后骨关节炎（OA）的发病机理，或者可能会抑制骨软骨移植后的愈合，这是需要修复软骨的恢复程序一系列机械冲击以插入移植物。因此，有必要了解哪些因素会影响原位的脆弱性。软骨细胞受到机械性损伤。为此，本研究的目的是研究通过不同方式（静水压，单轴负荷和渗透挑战，有无调节体积减小的抑制作用）改变细胞体积如何影响原位脆弱性。软骨细胞受到极大的机械力。使用定制的实验平台，能够测试活的和完整的鼠软骨对骨的外植体，我们建立了软骨细胞体积与易受伤害的脆弱性之间的强相关性，其中体积减小是有保护作用的。此外，我们发现体积扰动干预并不影响软骨ECM的机械性能，这表明它们对软骨细胞易损性的影响发生在细胞水平。这项研究的发现为旨在预防软骨软骨移植过程中软骨细胞丢失或阻止关节不稳定损伤后细胞死亡进程的新策略提供了新途径。