Guo Yanheng, Stampoultzis Theofanis, Nasrollahzadeh Naser, Karami Peyman, Rana Vijay Kumar, Applegate Lee, Pioletti Dominique P
Laboratory of Biomechanical Orthopedics, Institute of Bioengineering, EPFL, Lausanne, Switzerland.
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
iScience. 2023 Nov 22;26(12):108519. doi: 10.1016/j.isci.2023.108519. eCollection 2023 Dec 15.
Cartilage degeneration, typically viewed as an irreversible, vicious cycle, sees a significant reduction in two essential biophysical cues: the well-established hydrostatic pressure (HP) and the recently discovered transient temperature increase. Our study aimed to evaluate the combined influence of these cues on maintaining cartilage homeostasis. To achieve this, we developed a customized bioreactor, designed to mimic the specific hydrostatic pressure and transient thermal increase experienced during human knee physiological activities. This system enabled us to investigate the response of human 3D-cultured chondrocytes and human cartilage explants to either isolated or combined hydrostatic pressure and thermal stimuli. Our study found that chondroinduction (SOX9, aggrecan, and sulfated glycosaminoglycan) and chondroprotection (HSP70) reached maximum expression levels when hydrostatic pressure and transient thermal increase acted in tandem, underscoring the critical role of these combined cues in preserving cartilage homeostasis. These findings led us to propose a refined model of the vicious cycle of cartilage degeneration.
软骨退变通常被视为一个不可逆的恶性循环，其两个重要的生物物理信号会显著减少，即早已明确的静水压力（HP）和最近发现的短暂温度升高。我们的研究旨在评估这些信号对维持软骨内环境稳定的综合影响。为实现这一目标，我们开发了一种定制生物反应器，旨在模拟人类膝关节生理活动期间所经历的特定静水压力和短暂温度升高。该系统使我们能够研究人类三维培养软骨细胞和人类软骨外植体对单独或联合的静水压力和热刺激的反应。我们的研究发现，当静水压力和短暂温度升高协同作用时，软骨诱导（SOX9、聚集蛋白聚糖和硫酸化糖胺聚糖）和软骨保护（热休克蛋白70）达到最大表达水平，这突出了这些联合信号在维持软骨内环境稳定中的关键作用。这些发现促使我们提出了一个关于软骨退变恶性循环的改进模型。
