Next Article in Journal
Allosteric Binding Sites On Nuclear Receptors: Focus On Drug Efficacy and Selectivity
Previous Article in Journal
Components from the Human c-myb Transcriptional Regulation System Reactivate Epigenetically Repressed Transgenes
Open AccessArticle

Increasing the Medium Osmolarity Reduces the Inflammatory Status of Human OA Chondrocytes and Increases Their Responsiveness to GDF-5

1
Osteoarthritis Research, Merck KGaA, 64293 Darmstadt, Germany
2
Institute for Organic Chemistry and Biochemistry, Technische Universität, 64287 Darmstadt, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(2), 531; https://doi.org/10.3390/ijms21020531
Received: 18 November 2019 / Revised: 9 January 2020 / Accepted: 11 January 2020 / Published: 14 January 2020
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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. View Full-Text
Keywords: osmolarity; osteoarthritis; chondrocytes; growth and differentiation factor-5 (GDF-5) osmolarity; osteoarthritis; chondrocytes; growth and differentiation factor-5 (GDF-5)
Show Figures

Figure 1

MDPI and ACS Style

Mang, T.; Lindemann, S.; Gigout, A. Increasing the Medium Osmolarity Reduces the Inflammatory Status of Human OA Chondrocytes and Increases Their Responsiveness to GDF-5. Int. J. Mol. Sci. 2020, 21, 531.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop