acid-phosphatase and Chondrocalcinosis

Bone destruction is a common feature of inflammatory arthritis and is mediated by osteoclasts, the only specialized cells to carry out bone resorption. Aberrant expression of receptor activator of nuclear factor kappa β ligand (RANKL), an inducer of osteoclast differentiation has been linked with bone pathology and the synovial fibroblast in rheumatoid arthritis (RA). In this manuscript, we challenge the current concept that an increase in RANKL expression governs osteoclastogenesis and bone destruction in autoimmune arthritis. We isolated human fibroblasts from RA, pyrophosphate arthropathy (PPA) and osteoarthritis (OA) patients and analyzed their RANKL/OPG expression profile and the capacity of their secreted factors to induce osteoclastogenesis. We determined a 10-fold increase of RANKL mRNA and protein in fibroblasts isolated from RA relative to PPA and OA patients. Peripheral blood mononuclear cells (PBMC) from healthy volunteers were cultured in the presence of RA, PPA and OA synovial fibroblast conditioned medium. Osteoclast differentiation was assessed by expression of tartrate-resistant acid phosphatase (TRAP), vitronectin receptor (VNR), F-actin ring formation and bone resorption assays. The formation of TRAP(+), VNR(+) multinucleated cells, capable of F-actin ring formation and lacunar resorption in synovial fibroblast conditioned medium cultures occured in the presence of osteoprotegerin (OPG) a RANKL antagonist. Osteoclasts did not form in these cultures in the absence of macrophage colony stimulating factor (M-CSF). Our data suggest that the conditioned medium of pure synovial fibroblast cultures contain inflammatory mediators that can induce osteoclast formation in human PBMC independently of RANKL. Moreover inhibition of the TNF or IL-6 pathway was not sufficient to abolish osteoclastogenic signals derived from arthritic synovial fibroblasts. Collectively, our data clearly show that alternate osteoclastogenic pathways exist in inflammatory arthritis and place the synovial fibroblast as a key regulatory cell in bone and joint destruction, which is a hallmark of autoimmune arthritis.

Topics: Acid Phosphatase; Actins; Arthritis, Rheumatoid; Bone Resorption; Cell Differentiation; Cells, Cultured; Chondrocalcinosis; Culture Media, Conditioned; Fibroblasts; Gene Expression Regulation; Humans; Integrin alphaVbeta3; Interleukin-6; Isoenzymes; Leukocytes, Mononuclear; Osteoarthritis; Osteoclasts; Osteoprotegerin; RANK Ligand; Signal Transduction; Synovial Fluid; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factor-alpha

This paper describes a morphologic, quantitative, cytochemical study of mononuclear non lymphoid cells in knee synovial fluid in osteoarthritis and various arthritides. Morphologic criteria allow to identify among these cells various synoviocytic and monocytic subtypes with in both types, phagocytic subtypes. Quantitative study shows in arthritides an important afflux of monocytes and a hyperexfoliation of synoviocytes. In fluids with intermediate cellularity, Monocytes/Synoviocytes ratio allows the differential cytodiagnosis between osteoarthrosis and arthritis. All monocytic subtypes and especially the phagocytic one are highly significantly increased in arthritides. Synoviocytic subtypes show a lower increase, except the phagocytic one, which is not changed. Giant multinuclear synoviocytes are found in every type of disease and cannot constitute a cytodiagnosis marker. Alcian Blue and hyaluronidase treatment show hyaluronate in a few percentage of Synoviocytes. Cytoenzymologic study shows that synoviocytes and monocytes are positive in all tested hydrolases: beta Glucuronidase, Acid Phosphatase, alpha Naphthyl Acetate Esterase, these activities being always higher in synoviocytes. With peroxidase, synoviocytes are always negative, so this reaction although it marks only a minority of monocytic population can be used as an extra cytologic criterion for discrimination of mononuclear cells in synovial fluid. In these four enzymes there is no significant quantitative difference at cellular level between osteoarthrosis and arthritides. Lysosomal enzymatic activity in both monocytic and synoviocytic cells confirms their heterophagic properties. However synoviocytic heterophagy seems to be a physiological process not or few affected by inflammatory events. On the opposite, monocytic heterophagy and then macrophagic transformation of monocytes appears as a major aspect of intrasynovial inflammatory reaction. If a large majority of exfoliated synoviocytes comes from A type synovial lining cells and if they belong to Mononuclear Phagocyte System, why do they so weakly, or not, participate as phagocytes to inflammatory reaction.

Topics: Acid Phosphatase; Arthritis, Reactive; Arthritis, Rheumatoid; Chondrocalcinosis; Glucuronidase; Gout; Humans; Joint Diseases; Knee Joint; Naphthol AS D Esterase; Peroxidases; Spondylitis, Ankylosing; Synovial Fluid

Topics: Acid Phosphatase; Aminosalicylic Acids; Arthritis, Rheumatoid; Chondrocalcinosis; Enzymes; Esterases; Exudates and Transudates; Glucuronidase; Histocytochemistry; Humans; Knee Joint; Lymphocyte Activation; Lymphocytes; Monocytes; Naphthalenes; Osteoarthritis; Osteochondritis; Punctures; Rheumatic Diseases; Synovial Fluid

Topics: Acid Phosphatase; Alkaline Phosphatase; Arthritis, Reactive; Behcet Syndrome; Buffers; Chondrocalcinosis; Gout; Histocytochemistry; Humans; Hydrarthrosis; Joint Diseases; Methods; Synovial Fluid; Ultracentrifugation

Topics: Acid Phosphatase; Chondrocalcinosis; Diphosphates; Female; Gout; Hemolysis; Humans; Inflammation; Leukocytes; Lysosomes; Male; Membranes; Phagocytosis; Sex Factors; Silicon Dioxide; Uric Acid