Endoplasmic reticulum stress inhibits collagen synthesis independent of collagen-modifying enzymes in different chondrocyte populations and dermal fibroblasts.
Chondrocytes respond to glucose deprivation with a decreased collagen synthesis due to disruption of a proper functioning of the endoplasmic reticulum (ER): ER stress. Since the mechanisms involved in the decreased synthesis are unknown, we have investigated whether chaperones and collagen-modifying enzymes are affected by glucose deprivation. Chondrocytes obtained from nucleus pulposus, annulus fibrosus, articular cartilage, and meniscus and dermal fibroblasts were cultured under control conditions or exposed to the ER stress-inducing treatments of tunicamycin addition or glucose withdrawal. Both treatments resulted in an up-regulation of the gene expression of the ER stress markers in all cell types, but dermal fibroblasts showed a delayed response to glucose deprivation. Collagen gene expression was down-regulated, and less collagen protein was present in the cells under both ER stress-inducing conditions. The expression levels of the prolyl 4-hydroxylases were either not affected (P4ha3) or increased (P4ha1 and P4ha2), the levels of the lysyl hydroxylases decreased, and the N-propeptidase Adamts2 decreased. Both treatments induced apoptosis. Chondrocytes respond more quickly to glucose deprivation, but it appears that chondrocytes can cope better with tunicamycin-induced ER stress than fibroblasts. Although collagen synthesis was inhibited by the treatments, some collagen-modifying enzymes and chaperones were up-regulated, suggesting that there is no causal relation between them.
Vonk
Lucienne A
LA
Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Research Institute MOVE, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Doulabi
Behrouz Zandieh
BZ
Huang
Chun-Ling
CL
Helder
Marco N
MN
Everts
Vincent
V
Bank
Ruud A
RA
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002356:Cartilage / Q000166:cytology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D003094:Collagen / Q000096:biosynthesis* / Q000378:metabolism; D020405:Dermis / Q000166:cytology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D013312:Stress, Physiological
D003094:Collagen