Gadolinium meglumime contributes to chondrocyte hypertrophy through up-regulating the expression of type X collagen and extracellular matrix remodeling protease MMPs and ADAMTs
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AbstractObjective: Gadoterate meglumine (trade names Dotarem and Artirem) is a macrocyclic gadolinium based contrast agent (GBCA) used in angiography and arthrography. It has been found that the use of some linear GBCAs could induce nephrogenic systemic fibrosis (NSF) in patients with renal deficiency. Although gadoterate meglumine has a higher safety profile among GBCAs and no new cases of NSF have been reported since 2009 after the application
of safer GBCAs and cautious use in patients with renal problems, the question on how GBCAs induce a systemic fibrotic pathological change to dermal and internal connective tissues remains largely unanswered. And there are still concerns over accumulated gadolinium after repeated GBCA-contrasted MRI. We aim at revealing possible pathological effects that gadoterate meglumine could make to cartilage chondrocytes.
Methods: Chondrocytes from coastal cartilage of neonatal mice rib cages were isolated and expanded in vitro for micromass cell culture. Alcian blue staining of micromass was done to assess proteoglycan production. Chondrocyte marker gene expression was evaluated by qPCR. CCK-8 assay was conducted to check the influence of gadoterate meglumine on chondrocyte viability and/or proliferation.
Results: At sub-clinical concentrations as low as 10nM and supra-clinical concentrations as high as 100μM, gadoterate meglumine increased hypertrophic marker gene expression including Col10a1, MMPs and ADAMTs. But its effect on proteoglycan production was not obviously seen in the Alcian blue staining. In the CCK-8 assay, gadoterate meglumine increased chondrocyte viability and/or proliferation at high concentrations.
Conclusion: Gadoterate meglumine could promote chondrocyte hypertrophy-related gene expression in chondrocytes. Further experiments on protein expression are still needed to confirm its effect on chondrocyte hypertrophy. More research should also be done on how freegadolinium could affect calcium-activated enzymes and receptors in order to elucidate the underlying mechanisms.
Acceptance Date10/12/2019
All Author(s) ListLingxiao Liu, Wing Pui Tsang, Fengjie Zhang, Chao Wan
Name of Conference2019 Guangzhou-Hong Kong Postgraduate Research Exchange and Symposium on Regenerative Medicine
Start Date of Conference10/12/2019
End Date of Conference11/12/2019
Place of ConferenceGuangzhou
Country/Region of ConferenceChina
Year2019
Month12
LanguagesEnglish-United Kingdom
KeywordsGadoterate meglumine; chondrocyte hypertrophy; cartilage

Last updated on 2020-27-11 at 16:46