Osteoarthritis Research, Merck KGaA, 64293 Darmstadt, Germany.
Institute for Organic Chemistry and Biochemistry, Technische Universität, 64287 Darmstadt, Germany.
Int J Mol Sci. 2020 Jan 14;21(2):531. doi: 10.3390/ijms21020531.
The environment surrounding chondrocytes changes drastically in osteoarthritis (OA). For instance, the osmolarity in cartilage (ranging from 350 to 460 mOsm in healthy tissue) decreases during the progression of OA, reaching 270 mOsm. The objective of this study was to evaluate how osmolarity influences human OA chondrocytes. For this purpose, the osmolarity of the culture medium (340 mOsm) was increased to 380, 420 or 460 mOsm and its effect on the phenotype, matrix production, protease expression, cytokine release and growth and differentiation factor-5 (GDF-5) receptor expression in human OA chondrocytes was evaluated in a monolayer. Afterwards, the same parameters, as well as the responsiveness to GDF-5, were evaluated in 3D culture at 340 and 380 mOsm. Our results revealed that increasing the medium osmolarity increased matrix production but also reduced cytokine release, type I collagen and protease expression. It was also demonstrated that at 380 mOsm, the response to GDF-5 in 3D culture was more robust than at 340 mOsm. For the first time, it was established that a decreased osmolarity plays a role in sustaining inflammation and catabolic activities in OA chondrocytes and decreases their responsiveness to GDF-5. This indicates that osmolarity is a critical aspect of OA pathobiology.
软骨细胞所处的环境在骨关节炎（OA）中会发生剧烈变化。例如，软骨中的渗透压（健康组织中范围在 350 至 460mOsm 之间）在 OA 进展过程中会降低，达到 270mOsm。本研究旨在评估渗透压如何影响人 OA 软骨细胞。为此，将培养基的渗透压（340mOsm）升高至 380、420 或 460mOsm，并在单层培养中评估其对人 OA 软骨细胞表型、基质产生、蛋白酶表达、细胞因子释放以及生长和分化因子-5（GDF-5）受体表达的影响。之后，在 340 和 380mOsm 下的 3D 培养中评估了相同的参数以及对 GDF-5 的反应性。研究结果表明，增加培养基渗透压会增加基质产生，但也会降低细胞因子释放、I 型胶原和蛋白酶表达。还证明在 380mOsm 下，3D 培养中对 GDF-5 的反应比在 340mOsm 下更强烈。本研究首次证实，降低渗透压会在 OA 软骨细胞中维持炎症和分解代谢活性，并降低其对 GDF-5 的反应性。这表明渗透压是 OA 病理生物学的一个关键方面。
