A novel role for Bcl-2 associated-athanogene-1 (Bag-1) in regulation of the endoplasmic reticulum stress response in mammalian chondrocytes.
BAG-1 (Bcl-2 associated athanogene-1) is a multifunctional protein, linking cell proliferation, cell death, protein folding, and cell stress. In vivo, BAG-1 is expressed in growth plate and articular cartilage, and the expression of BAG-1 is decreased with aging. Chondrocytes respond to endoplasmic reticulum (ER) stress with decreased expression of extracellular matrix proteins, and prolonged ER stress leads to chondrocyte apoptosis. Here we demonstrate for the first time that BAG-1 is involved in ER stress-induced apoptosis in chondrocytes. Induction of ER stress through multiple mechanisms all resulted in downregulation of BAG-1 expression. In addition, direct suppression of BAG-1 expression resulted in chondrocyte growth arrest and apoptosis, while stable overexpression of BAG-1 delayed the onset of ER stress-mediated apoptosis. In addition to regulating apoptosis, we also observed decreased expression of collagen type II in BAG-1 deficient chondrocytes. In contrast, overexpression of BAG-1 resulted in increased expression of collagen type II. Moreover, under ER stress conditions, the reduced expression of collagen type II was delayed in chondrocytes overexpressing BAG-1. These results suggest a novel role for BAG-1 in supporting viability and matrix expression of chondrocytes.
Yang
Ling
L
Department of Anatomy, Northeastern Ohio Universities College of Medicine, 4209 State Route 44, Rootstown, Ohio 44272, USA.
McBurney
Denise
D
Tang
Shou-Ching
SC
Carlson
Sara G
SG
Horton
Walter E
WE
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D024043:Collagen Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D008954:Models, Biological; D010641:Phenotype; D034622:RNA Interference; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology; D014162:Transfection
C091732:BCL2-associated athanogene 1 protein; D024043:Collagen Type II; D004268:DNA-Binding Proteins; D014157:Transcription Factors