Open AccessRedifferentiation of aged human articular chondrocytes by combining bone morphogenetic protein-2 and melanoma inhibitory activity protein in 3D-culture
Author(s) -
Stephan Payr,
Brigitte Tichy,
Clemens Atteneder,
Mary Ellen Michel,
Thomas M. Tiefenboeck,
Nikolaus Lang,
Sylvia Nuernberger,
Stefan Hajdu,
Elizabeth R. Balmayor,
Stefan Marlovits,
Christian Albrecht
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0179729
Subject(s) - bone morphogenetic protein , glycosaminoglycan , bone morphogenetic protein 2 , bone morphogenetic protein 6 , mesenchymal stem cell , alkaline phosphatase , bone morphogenetic protein 7 , chemistry , cartilage , calcification , aggrecan , type ii collagen , microbiology and biotechnology , andrology , medicine , in vitro , pathology , biology , osteoarthritis , biochemistry , anatomy , articular cartilage , enzyme , alternative medicine , gene
Melanoma inhibitory activity (MIA) affects the differentiation to hyaline cartilage and can inhibit the osteogenic potential of bone morphogenetic protein (BMP)-2 in mesenchymal stem cells (MSC). The aim of this study was to investigate if MIA also inhibits the osteogenic potential of BMP-2 in human articular chondrocytes during redifferentiation, which may lead to a higher grade of differentiation without calcification. HAC of four female patients (mean age: 73.75 ±6.98) were seeded into 3D culture for 28 days; after adding the recombinant proteins, four groups were formed (Control, BMP-2, MIA, BMP-2+MIA). Samples were analysed for gene expression, glycosaminoglycan (GAG) content and histology on day 0, 14 and 28. Collagen type 2 ( COL2A1 ) was significantly increased in the BMP-2 containing groups on day 28; BMP-2 (100-fold, p = 0.001), BMP-2+MIA (65-fold, p = 0.009) and similar to the level of native cartilage. Higher aggrecan ( Agg ) levels were present in the BMP-2 (3-fold, p = 0.007) and BMP-2+MIA (4-fold, p = 0.002) group after 14 days and in the BMP-2 (9-fold, p = 0.001) group after 28 days. Collagen type 10 ( COL10A1 ) was increased in the BMP-2 containing groups (6-fold, p = 0.006) but these levels were significantly below native cartilage. Alkaline phosphatase ( ALP ), collagen type 1 ( COL1A1 ) and the glycosaminoglycan (GAG) content did not reveal any relevant differences between groups. BMP-2 is a potent inducer for differentiation of HAC. A significant enhancement of this effect in combination with MIA could not be observed. Furthermore no significant reduction of osteogenic markers during re-differentiation of chondrocytes was present combining BMP-2 and MIA.