PT  - JOURNAL ARTICLE
AU  - Jami Mandelin
AU  - Tian-Fang Li
AU  - Mika Hukkanen
AU  - Mikko Liljeström
AU  - Jari Salo
AU  - Seppo Santavirta
AU  - Yrjö T Konttinen
TI  - Interface tissue fibroblasts from loose total hip replacement prosthesis produce receptor activator of nuclear factor-kappaB ligand, osteoprotegerin, and cathepsin K.
DP  - 2005 Apr 01
TA  - The Journal of Rheumatology
PG  - 713--720
VI  - 32
IP  - 4
4099  - http://www.jrheum.org/content/32/4/713.short
4100  - http://www.jrheum.org/content/32/4/713.full
SO  - J Rheumatol2005 Apr 01; 32
AB  - OBJECTIVE: The highly osteolytic interface tissue between the bone and loosening total hip prosthesis is characterized by low pH, formation of foreign body giant cells, osteoclasts, and production of receptor activator of nuclear factor-kappaB (RANKL) and cathepsin K. We hypothesized that fibroblasts in the interface tissue may form a source for RANKL production. METHODS: Primary interface tissue fibroblasts, fibrous joint capsule fibroblasts, and trabecular bone osteoblasts were stimulated with tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), IL-6, IL-11, or 1alpha,25-(OH)2 vitamin D3. Cellular RANKL and released cathepsin K were detected by Western blotting. RANKL in cell lysates and osteoprotegerin (OPG) in cell culture medium were measured by ELISA. RANKL, OPG, and cathepsin K mRNA were measured with quantitative reverse transcriptase polymerase chain reaction. RESULTS: Interface tissue fibroblasts were found to produce RANKL. 1alpha,25-(OH)2 vitamin D3 stimulation increased RANKL mRNA expression. TNF-alpha was found to be the most potent OPG inducer in interface tissue fibroblasts. Cathepsin K mRNA production in fibroblasts was upregulated roughly 3-fold (p < 0.01) after 1alpha,25-(OH)2D3 stimulation, and both pro- and active cathepsin K protein was released to fibroblast culture media. CONCLUSION: Interface tissue fibroblasts are able to produce RANKL, OPG, and cathepsin K and may contribute indirectly and directly to pathologic periprosthetic collagenolysis and bone destruction.