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Sci Rep. 2017 Jun 16;7(1):3708. doi: 10.1038/s41598-017-03958-5.

Rho-kinase inhibitor Y-27632 and hypoxia synergistically enhance chondrocytic phenotype and modify S100 protein profiles in human chondrosarcoma cells.

Author information

1
Department of Integrative Medical Biology, Umeå University, Linnaeus väg 9, 90187, Umeå, Sweden.
2
Computational Life Science Cluster (CLiC), Department of Chemistry, Umeå University, Linnaeus väg 10, 90187, Umeå, Sweden.
3
Department of Integrative Medical Biology, Umeå University, Linnaeus väg 9, 90187, Umeå, Sweden. mikko.lammi@umu.se.
4
School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, China. mikko.lammi@umu.se.

Abstract

Articular chondrocytes are slowly dividing cells that tend to lose their cell type-specific phenotype and ability to produce structurally and functionally correct cartilage tissue when cultured. Thus, culture conditions, which enhance the maintenance of chondrocyte phenotype would be very useful for cartilage research. Here we show that Rho-kinase inhibition by Y-27632 under hypoxic conditions efficiently maintains and even enhances chondrocyte-specific extracellular matrix production by chondrocytic cells. The effects of long-term Y-27632 exposure to human chondrosarcoma 2/8 cell phenotype maintenance and extracellular matrix production were studied at normoxia and at a 5% low oxygen atmosphere. Y-27632 treatment at normoxia induced ACAN and COL2A1 gene up-regulation and a minor increase of sulfated glycosaminoglycans (sGAGs), while type II collagen expression was not significantly up-regulated. A further increase in expression of ACAN and COL2A1 was achieved with Y-27632 treatment and hypoxia. The production of sGAGs increased by 65.8%, and ELISA analysis revealed a 6-fold up-regulation of type II collagen. Y-27632 also induced the up-regulation of S100-A1 and S100-B proteins and modified the expression of several other S100 protein family members, such as S100-A4, S100-A6, S100-A13 and S100-A16. The up-regulation of S100-A1 and S100-B proteins is suggested to enhance the chondrocytic phenotype of these cells.

PMID:
28623370
PMCID:
PMC5473921
DOI:
10.1038/s41598-017-03958-5
[Indexed for MEDLINE]
Free PMC Article

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