Advanced osteoarthritis in humans is associated with altered collagen VI expression and upregulation of ER-stress markers Grp78 and bag-1.

Advanced osteoarthritis in humans is associated with altered collagen VI expression and upregulation of ER-stress markers Grp78 and bag-1.

Nugent Ashleigh E; Speicher Danielle M; Gradisar Ian; McBurney Denise L; Baraga Anthony; Doane Kathleen J; Horton Walter E Jr

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society

2009

2009-10

To test the hypothesis that a perturbation of endoplasmic reticulum (ER) function is involved in the pathogenesis of osteoarthritis (OA), articular cartilage was isolated from non-OA patients secondary to resection of osteo- or chondrosarcomas. Intra-joint samples of minimal and advanced osteoarthritic cartilage were isolated from patients undergoing total knee arthroplasty and scored for disease severity. Glucose-regulated protein-78 (grp78) and bcl-2-associated athanogene-1 (bag-1) were detected via immunofluorescence as markers of non-homeostatic ER function. Additionally, the expression of type VI collagen and its integrin receptor, NG2, was determined to examine cartilage matrix health and turnover. There was an upregulation of grp78 in advanced OA, and variable expression in minimal OA. Non-OA cartilage was consistently grp78 negative. The downstream regulator bag-1 was also upregulated in OA compared with normal cartilage. Collagen VI was mainly cell-associated in non-OA cartilage, with a more widespread distribution observed in OA cartilage along with increased intracellular staining intensity. The collagen VI integral membrane proteoglycan receptor NG2 was downregulated in advanced OA compared with its patient-matched minimally involved cartilage sample. These results suggest that chondrocytes exhibit ER stress during OA, in association with upregulation of a large secreted molecule, type VI collagen.

Adult; Humans; Middle Aged; Osteoarthritis; Biomarkers/metabolism; Proteoglycans/biosynthesis; Down-Regulation; Up-Regulation; Cartilage; Antigens/biosynthesis; Bone Neoplasms/metabolism; Chondrosarcoma/metabolism; Collagen Type VI/*biosynthesis; DNA-Binding Proteins/*biosynthesis; Endoplasmic Reticulum/*metabolism; Heat-Shock Proteins/*biosynthesis; Osteosarcoma/metabolism; Transcription Factors/*biosynthesis; Articular/metabolism; Knee/*metabolism/physiopathology

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923–931

10

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