11β-Hydroxysteroid Dehydrogenase Type 1 Expression in Periprosthetic Osteolysis

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Abstract

abstract

Membranes surrounding loosened total joint implants contain predominantly fibroblasts along with macrophages and various cytokines including IL-1β and TNF-α. Glucocorticoids inhibit osteoblast proliferation and protein synthesis. Local levels of glucocorticoids result from peripheral conversion to an active form by the enzyme 11 β-hydroxysteroid dehydrogenase type 1 (11 β-HSD1). Glucorticoids may play an inhibitory role of osteoblast function in osteolysis through the upregulation 11 β-HSD1 in membrane fibroblasts by IL-1β and TNF-α.

IL1-β and TNF-α were added to fibroblast cell cultures at 0, 5, and 25 ng/mL and total RNA was isolated at 12 hours. TNF-α was added to fibroblast cell cultures at a concentration of 5 ng/mL and total RNA was isolated at 1, 6, and 24 hours. Real-time polymerase chain reaction was used to quantify 11 β-HSD1 gene expression. Also, 15 periprosthetic membrane samples from loosened total joint implants secondary to osteolysis were analyzed for the presence of 11 β-HSD1 gene expression using immunohistochemistry.

11β-HSD1 gene expression was significantly upregulated after addition of IL1-β and TNF-α to fibroblast cell cultures. Increased 11 β-HSD1 gene expression also resulted with increasing exposure time to TNF-α at a concentration of 5 ng/mL. The 15 periprosthetic membrane samples from loosened total joints secondary to osteolysis were all found to have increased 11 β-HSD1 gene expression compared to control tissue. Both macrophages and fibroblasts were found to have upregulation.

We provide preliminary evidence that 11β-HSD1 is expressed in periprosthetic membranes and that TNF-α and IL-1β upregulate fibroblast expression of the glucocorticoid converting enzyme 11 β-HSD1.

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