Inflammatory microcrystals alter the functional phenotype of human osteoblast-like cells in vitro: synergism with IL-1 to overexpress cyclooxygenase-2.
Chronic crystal-associated arthropathies such as gout and pseudogout can lead to local bone destruction. Because osteoblasts, which orchestrate bone remodeling via soluble factors and cell-to-cell interactions, have been described in contact with microcrystals, particularly in uratic foci of gout, we hypothesized that microcrystals of monosodium urate monohydrate (MSUM) and of calcium pyrophosphate dihydrate (CPPD) could alter osteoblastic functions. MSUM and CPPD adhered to human osteoblastic cells (hOB) in vitro and were partly phagocytized as shown by scanning electron microscopy. MSUM and CPPD dose-dependently stimulated the production of PGE(2) in hOB as assessed by enzyme immunoassay, a response that was synergistically enhanced in the presence of IL-1. The mechanism of this synergism was, at least in part, at the level of the expression of cyclooxygenase-2 as evaluated by immunoblot analysis. MSUM and CPPD also stimulated the expression of IL-6 and IL-8 and reduced the 1,25-dihydroxyvitamin D(3)-induced activity of alkaline phosphatase and osteocalcin in hOB (with no synergism with IL-1). MSUM- or CPPD-stimulated expression of IL-6 in hOB pretreated with the selective cyclooxygenase-2 inhibitor NS-398 was increased, unlike that induced by IL-1 alone which was partially reduced. MSUM-, CPPD- or IL-1-induced expression of IL-8 was unchanged by pretreating hOB with NS-398. These results suggest that inflammatory microcrystals alter the normal phenotype of hOB, redirecting them toward reduced bone formation and amplified osteoblast-mediated bone resorption, abnormalities that could play a role in the bone destruction associated with chronic crystal-induced arthritis.
Bouchard
Line
L
Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du Pavillon Centre Hospitalier de l'Université Laval, Department of Medicine, Université Laval, 2705 Boulevard Laurier, Ste-Foy, Québec, Canada G1V 4G2.
de Médicis
Rinaldo
R
Lussier
André
A
Naccache
Paul H
PH
Poubelle
Patrice E
PE
D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000502:physiology; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D002131:Calcium Pyrophosphate / Q000009:adverse effects*; D002478:Cells, Cultured; D003460:Crystallization; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D007375:Interleukin-1 / Q000009:adverse effects / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D008855:Microscopy, Electron, Scanning; D010006:Osteoblasts / Q000201:enzymology / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure; D015675:Osteocalcin / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D014527:Uric Acid / Q000009:adverse effects*
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D007527:Isoenzymes; D008565:Membrane Proteins; D015675:Osteocalcin; D014527:Uric Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000469:Alkaline Phosphatase; D015232:Dinoprostone; D002131:Calcium Pyrophosphate