Ostasis.Extracellular MatrixCollagen II and Proteoglycans. The extracellular matrix proteins collagen II and proteoglycans were investigated most frequently in response to CTS, corresponding to their prominent appearance among all proteins in articular cartilage. Several of the selected studies deal with the effect of CTS on collagen II (n = 9) and aggrecan (n = 11) at the mRNA level. The total collagen synthesis was measured by [2,3- ]proline incorporation and was investigated in two cases [23,25]. One study analyzed collagen II at the protein level using immunostaining of chondrocytes after CTS [34]. None of the other collagens prominent in cartilage (e. g. collagen III, V, VI, IX, X, XI, XII, and XIV) [43,44] have yet been investigated in response to CTS. In three articles, the cartilage-unspecific gene collagen I [45] or the hypertrophy-associated gene collagen X [24,26] were analyzed, but only to control the phenotype and dedifferentiation state of the chondrocytes. The total proteoglycan synthesis was measured as incorporation of [35S]labeled proteoglycans into the cells and the medium (n = 10). One study analyzed biglycan and versican [27]. However, no effects of CTS on the mRNA levels of these two proteins were observed. Other GAGs or proteoglycans, like decorin, fibromodulin and lumican were not yet investigated in response to CTS. Interestingly, the response PX-478 site pattern of collagen II and proteoglycans to CTS were similar and therefore were discussed simultaneously in the following. Furthermore, the results of collagen II and proteoglycans are sorted according to thePLOS ONE | DOI:10.1371/journal.pone.0119816 March 30,9 /Cyclic Tensile Strain and Chondrocyte MetabolismTable 3. Effects of STC on collagen II and aggrecan mRNA. Loading duration 0.5 h 1h 3h Strain magnitude 7.5 7.5 10 10 7 10 24 6h 7 7 10 12 h 7 7 7 10 10 16 16 h 18 h 24 h 7 7 6 7 7 7 10 10 16 36 h 48 h 72 h 7 6 16 6 Frequency 1 Hz 1 Hz 0.5 Hz 0.17 Hz 0.5 Hz 0.5 Hz 0.25 Hz 0.5 Hz 0.5 Hz 0.17 Hz 0.5 Hz 0.5 Hz 0.5 Hz 0.5 Hz 0.17 Hz 0.5 Hz 0.5 Hz 0.5 Hz 0 05 Hz 0.5 Hz 0.5 Hz 0.5 Hz 0.5 Hz 0.17 Hz 0.5 Hz 0.5 Hz 0.05 Hz 0.5 Hz 0.05 Hz Collagen II mRNA level “a b ” ” “b ” # #b # # # # # #b # Aggrecan mRNA level “a b ” ” “b b # # # # #b Reference [46] [46] [37] [13] [38] [37] [14] [33] [38] [13] [33] [38] [36] [37] [13] [26] [33] [36] [27] [33] [38] [36] [37] [13] [26] [38] [27] [26] [27]Effects of CTS on collagen II and aggrecan mRNA level in articular chondrocytes, sorted by loading duration # mRNA levels of loaded cells were decreased relative to unloaded cells mRNA levels of loaded cells were unchanged relative to unloaded cells ” mRNA levels of loaded cells were increased relative to unloaded cellsa bmRNA levels measured after a 4 h recovery instead of immediately after the loading mRNA levels after loading were compared to levels before loadingdoi:10.1371/journal.pone.0119816.tloading duration, since this parameter seemed to influence the cellular response to CTS substantially. Collagen II and Proteoglycans–RNA Level. Compared to unloaded cells [37,46] and to mRNA levels before loading [13], collagen II and aggrecan were not ABT-737 site altered after loading regimes that were shorter than 60 min (Table 3). However, Thomas et al. (2011) made an interesting observation: Immediately after a 30 min loading, mRNA levels were not changed compared to those of unloaded cells [46]. However, after a recovery of 4 h after the load.Ostasis.Extracellular MatrixCollagen II and Proteoglycans. The extracellular matrix proteins collagen II and proteoglycans were investigated most frequently in response to CTS, corresponding to their prominent appearance among all proteins in articular cartilage. Several of the selected studies deal with the effect of CTS on collagen II (n = 9) and aggrecan (n = 11) at the mRNA level. The total collagen synthesis was measured by [2,3- ]proline incorporation and was investigated in two cases [23,25]. One study analyzed collagen II at the protein level using immunostaining of chondrocytes after CTS [34]. None of the other collagens prominent in cartilage (e. g. collagen III, V, VI, IX, X, XI, XII, and XIV) [43,44] have yet been investigated in response to CTS. In three articles, the cartilage-unspecific gene collagen I [45] or the hypertrophy-associated gene collagen X [24,26] were analyzed, but only to control the phenotype and dedifferentiation state of the chondrocytes. The total proteoglycan synthesis was measured as incorporation of [35S]labeled proteoglycans into the cells and the medium (n = 10). One study analyzed biglycan and versican [27]. However, no effects of CTS on the mRNA levels of these two proteins were observed. Other GAGs or proteoglycans, like decorin, fibromodulin and lumican were not yet investigated in response to CTS. Interestingly, the response pattern of collagen II and proteoglycans to CTS were similar and therefore were discussed simultaneously in the following. Furthermore, the results of collagen II and proteoglycans are sorted according to thePLOS ONE | DOI:10.1371/journal.pone.0119816 March 30,9 /Cyclic Tensile Strain and Chondrocyte MetabolismTable 3. Effects of STC on collagen II and aggrecan mRNA. Loading duration 0.5 h 1h 3h Strain magnitude 7.5 7.5 10 10 7 10 24 6h 7 7 10 12 h 7 7 7 10 10 16 16 h 18 h 24 h 7 7 6 7 7 7 10 10 16 36 h 48 h 72 h 7 6 16 6 Frequency 1 Hz 1 Hz 0.5 Hz 0.17 Hz 0.5 Hz 0.5 Hz 0.25 Hz 0.5 Hz 0.5 Hz 0.17 Hz 0.5 Hz 0.5 Hz 0.5 Hz 0.5 Hz 0.17 Hz 0.5 Hz 0.5 Hz 0.5 Hz 0 05 Hz 0.5 Hz 0.5 Hz 0.5 Hz 0.5 Hz 0.17 Hz 0.5 Hz 0.5 Hz 0.05 Hz 0.5 Hz 0.05 Hz Collagen II mRNA level “a b ” ” “b ” # #b # # # # # #b # Aggrecan mRNA level “a b ” ” “b b # # # # #b Reference [46] [46] [37] [13] [38] [37] [14] [33] [38] [13] [33] [38] [36] [37] [13] [26] [33] [36] [27] [33] [38] [36] [37] [13] [26] [38] [27] [26] [27]Effects of CTS on collagen II and aggrecan mRNA level in articular chondrocytes, sorted by loading duration # mRNA levels of loaded cells were decreased relative to unloaded cells mRNA levels of loaded cells were unchanged relative to unloaded cells ” mRNA levels of loaded cells were increased relative to unloaded cellsa bmRNA levels measured after a 4 h recovery instead of immediately after the loading mRNA levels after loading were compared to levels before loadingdoi:10.1371/journal.pone.0119816.tloading duration, since this parameter seemed to influence the cellular response to CTS substantially. Collagen II and Proteoglycans–RNA Level. Compared to unloaded cells [37,46] and to mRNA levels before loading [13], collagen II and aggrecan were not altered after loading regimes that were shorter than 60 min (Table 3). However, Thomas et al. (2011) made an interesting observation: Immediately after a 30 min loading, mRNA levels were not changed compared to those of unloaded cells [46]. However, after a recovery of 4 h after the load.
