Effects of intermittent hydrostatic pressure and BMP-2 on osteoarthritic human chondrocyte metabolism in vitro.
ABSTRACT This study examined effects of intermittent hydrostatic pressure (IHP) and a chondrogenic growth factor, bone morphogenetic protein-2 (BMP-2), on anabolic, catabolic, and other metabolic markers in human osteoarthritic (OA) chondrocytes in vitro.
Articular chondrocytes, isolated from femoral OA cartilage and maintained in high-density monolayer culture, were examined for effects of BMP-2 and IHP on gene expression of matrix-associated proteins (aggrecan, type II collagen, and SOX9) and catabolic matrix metalloproteinases (MMP-2 and MMP-3) and culture medium levels of the metabolic markers MMP-2, nitric oxide (NO), and glycosaminoglycan (GAG). The results were analyzed using a mixed linear regression model to investigate the effects of load and growth factor concentration.
IHP and BMP-2 modulated OA chondrocyte metabolism in accordance with growth factor concentration independently, without evidence of synergism or antagonism. Each type of stimulus acted independently on anabolic matrix gene expression. Type II collagen and SOX9 gene expression were stimulated by both IHP and BMP-2 whereas aggrecan was increased only by BMP-2. IHP exhibited a trend to decrease MMP-2 gene expression as a catabolic marker whereas BMP-2 did not. NO production was increased by addition of BMP-2 and IHP exhibited a trend for increased levels. GAG production was increased by BMP-2.
This study confirmed the hypothesis that human OA chondrocytes respond to a specific type of mechanical load, IHP, through enhanced articular cartilage macromolecule gene expression and that IHP, in combination with a chondrogenic growth factor BMP-2, additively enhanced matrix gene expression without interactive effects.
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ABSTRACT: Regeneration of human cartilage is inherently inefficient. Current cell-based approaches for cartilage repair, including autologous chondrocytes, are limited by the paucity of cells, associated donor site morbidity and generation of functionally inferior fibrocartilage rather than articular cartilage. Upon investigating the role of Collagen VI (Col VI), a major component of the chondrocyte peri-cellular matrix (PCM), we observe that soluble Col VI stimulates chondrocyte proliferation. Interestingly, both adult and OA chondrocytes respond to soluble Col VI in a similar manner. The proliferative effect is however strictly due to the soluble Col VI as no proliferation is observed upon exposure of chondrocytes to immobilized Col VI. Upon short Col VI treatment in 2D monolayer culture, chondrocytes maintain high expression of characteristic chondrocyte markers like Col2a1, agc and Sox9 while the expression of the fibrocartilage marker Col I and of the hypertrophy marker Col X is minimal. Additionally, Col VI-expanded chondrocytes show a similar potential to untreated chondrocytes in engineering cartilage in 3D biomimetic hydrogel constructs. Our study has therefore identified soluble Col VI as a biologic that can be useful for expansion and utilization of scarce sources of chondrocytes, potentially for autologous chondrocyte implantation (ACI). Additionally, our results underscore the importance of further investigating the changes in chondrocyte PCM with age and disease and the subsequent effects on chondrocyte growth and function.Tissue Engineering Part A 09/2014; 21(3-4). DOI:10.1089/ten.TEA.2014.0375 · 4.07 Impact Factor
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ABSTRACT: The treatment of cartilage defects with matrix-embedded autologous chondrocytes is a promising method to support the repair process and to foster reconstitution of full functionality of the joint.Knee Surgery Sports Traumatology Arthroscopy 11/2014; 23(1). DOI:10.1007/s00167-014-3412-8 · 2.84 Impact Factor