Abstract
BackgroundRecent evidence indicates that osteoarthritis (OA) may be a systemic disease since mesenchymal stem cells (MSCs) from OA patients express type X collagen, a marker of late stage chondrocyte hypertrophy (associated with endochondral ossification). We recently showed that the expression of type X collagen was suppressed when MSCs from OA patients were cultured on nitrogen (N)-rich plasma polymer layers, which we call "PPE:N" (N-doped plasma-polymerized ethylene, containing up to 36 atomic percentage (at.% ) of N.MethodsIn the present study, we examined the expression of type X collagen in fetal bovine growth plate chondrocytes (containing hypertrophic chondrocytes) cultured on PPE:N. We also studied the effect of PPE:N on the expression of matrix molecules such as type II collagen and aggrecan, as well as on proteases (matrix metalloproteinase-13 (MMP-13) and molecules implicated in cell division (cyclin B2). Two other culture surfaces, "hydrophilic" polystyrene (PS, regular culture dishes) and nitrogen-containing cation polystyrene (Primaria®), were also investigated for comparison.ResultsResults showed that type X collagen mRNA levels were suppressed when cultured for 4 days on PPE:N, suggesting that type X collagen is regulated similarly in hypertrophic chondrocytes and in human MSCs from OA patients. However, the levels of type X collagen mRNA almost returned to control value after 20 days in culture on these surfaces. Culture on the various surfaces had no significant effects on type II collagen, aggrecan, MMP-13, and cyclin B2 mRNA levels.ConclusionHypertrophy is diminished by culturing growth plate chondrocytes on nitrogen-rich surfaces, a mechanism that is beneficial for MSC chondrogenesis. Furthermore, one major advantage of such "intelligent surfaces" over recombinant growth factors for tissue engineering and cartilage repair is potentially large cost-saving.
Highlights
Recent evidence indicates that osteoarthritis (OA) may be a systemic disease since mesenchymal stem cells (MSCs) from OA patients express type X collagen, a marker of late stage chondrocyte hypertrophy
We recently showed that a novel atmospheric-pressure plasma-polymerized thin film material, named “nitrogen-rich plasma-polymerized ethylene“ (PPE:N), is able to inhibit hypertrophy as well as osteogenesis in committed human MSCs from OA patients [6]
Neither aggrecan nor type I collagen expression were significantly affected. These results indicated that PPE:N coatings may be suitable surfaces for inducing MSCs to a chondrocyte or disc-like phenotype for tissue engineering of cartilage or intervertebral discs, respectively, in which hypertrophy and osteogenesis must be avoided
Summary
Recent evidence indicates that osteoarthritis (OA) may be a systemic disease since mesenchymal stem cells (MSCs) from OA patients express type X collagen, a marker of late stage chondrocyte hypertrophy (associated with endochondral ossification). Chondrocytes divide actively and synthesize different collagen molecules (types II, IX, and XI) and cartilage-specific proteoglycans [1,2,8] At this point in time, they express cell cycle-related genes such as cyclins [8]. The up-regulation of type X collagen expression signals the change in chondrocytic phenotype from prehypertrophic to hypertrophic, after which the matrix of the longitudinal septa between the cells starts to mineralize [2,8] This coordinated proliferation and differentiation of growth plate chondrocytes is required for normal growth and development of the skeleton [9,10,11,12,13,14]
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