Somatomedin activity in synovial fluid from patients with joint diseases.

Coates, Claire L.; Burwell, R. G.; Lloyd-Jones, K; Swannell, A J; Walker, G.; Selby, C.

doi:10.1136/ard.37.4.303

Cited by 21 publications

(6 citation statements)

References 32 publications

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“…If HA or CPPD crystals are indeed "competence"-promoting factors, they mpy be responsible for synovial cell proliferation in the crystal deposition diseases, since the factors in plasma needed for "progression" (such as somatomedin) are present in synovial fluid (26,27), which is largely a dialysis of plasma (28).…”

Section: Resultsmentioning

confidence: 99%

Mitogenic effects of hydroxyapatite and calcium pyrophosphate dihydrate crystals on cultured mammalian cells

Cheung

Story

McCarty

1984

Arthritis & Rheumatism

128

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Synthetic hydroxyapatite (HA) crystals in 1 % serum stimulated ' H thymidine uptake into quiescent canine synovial fibroblasts and human foreskin fibroblast cultures, as did 10% serum. The onset of stimulation and peak uptake of thymidine after crystal addition were delayed by 2-3 hours as compared with the effects produced by 10% serum. Stimulation of 'H thymidine uptake was proportional to the serum concentration used. HA crystals (50 pglml) stimulated nuclide uptake at each serum concentration used. 3H thymidine uptake was also proportional to the dose of HA or calcium pyrophosphate dihydrate crystals, although larger doses of the latter crystal were required to produce equivalent effects. Not all particulates were effective mitogenic agents. Latex beads and diamond crystals had no effect. Monosodium urate crystals modestly stimulated and calcium urate crystals markedly stimulated nuclide uptake. The more complex crystals found in a naturally occurring condition (calcinosis) were as mitogenic as the pure synthetic HA. The synovial cell hyperplasia sometimes associated with crystals might be explained in part by their mitogenic activity.

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Section: Resultsmentioning

confidence: 99%

Mitogenic effects of hydroxyapatite and calcium pyrophosphate dihydrate crystals on cultured mammalian cells

Cheung

Story

McCarty

1984

Arthritis & Rheumatism

128

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“…Few comparable data have been communicated so far. Coates et al [47] have reported on the effects of SF from three patients with RA and two with OA on porcine cartilage PG production in vitro, while Schalkwijk and associates [17], using bovine cartilage, have provided data on five patients with RA and two with OA. Due to small sample size, no differences between the respective groups were evident in either study.…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of insulin-like growth factor (IGF) binding protein-3 in rheumatoid arthritis synovial fluid inhibit stimulation by IGF-I of articular chondrocyte proteoglycan synthesis

Neidel

Blum²,

Schaeffer

et al. 1997

Rheumatology International

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The objective of this study was to quantify insulin-like growth factor (IGF) binding proteins (IGFBPs) in the synovial fluid (SF) and plasma of patients with rheumatic diseases and to study the role of these proteins in the regulation of cartilage proteoglycan (PG) synthesis. Immunological determination of IGFBP-2, IGFBP-3, IGF-I, IGF-II, interleukin-1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF alpha) was undertaken in the SF and plasma of 115 patients with rheumatoid arthritis (RA; n = 53), osteoarthritis (OA; n = 44) and other rheumatic disorders. We also determined the effects of SF on bovine cartilage PG synthesis in culture. IGFBP-2 and IGFBP-3 were elevated in the plasma (by 38% and 28%, respectively) and SF (by 56% and 59%, respectively) of patients with RA compared to age- and sex-matched OA controls (determined by RIA and confirmed by Western ligand blot). IGF-I and IGF-II did not differ significantly between the two groups. OA SF, and, to a lesser extent, RA SF stimulated cartilage PG synthesis in culture, and more than 60% of this activity was neutralised by a specific monoclonal anti-IGF-I antibody. Human IGFBP-3 dose-dependently inhibited the stimulation of cartilage PG synthesis effected by SF or human IGF-I. In RA patients, the SF concentration of IGFBP-3 was positively correlated with SF levels of IL-1 beta and TNF alpha, with the serum levels of C-reactive protein and with the erythrocyte sedimentation rate. We concluded that IGF-I is, under the conditions studied, the most important anabolic factor in human SF with respect to articular cartilage PG synthesis. The bioactivity of IGF-I in joints is modulated by IGFBP-3, which is elevated in RA SF compared to OA SF. Elevated IGFBP-3 in RA SF may reduce the availability of IGF-I to articular chondrocytes, thus interfering with cartilage PG synthesis in RA.

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“…Since previous studies have shown that 1) IGF-1 reduces the degradation of normal cartilage in vitro by its direct action on decreasing both the basal and the cytokine-stimulated degradation of proteoglycans (29,30), 2) serum IGF-1 levels appear to be reduced in OA (31) and in juvenile chronic arthritis (32), and 3) synovial fluid levels of IGF-1 are decreased in various arthritides (33), one may be tempted to conclude that a decrease in the availability of this anabolic factor may be responsible for the persistence of the osteoarthritic condition. However, recent findings showing the increased synthesis of IGF-1 by OA chondrocytes (34) combined with the enhancement of IGF-1 in the matrix and IGF-1 mRNA in chondrocytes of the superficial layer of human OA articular cartilage (35) render this hypothesis very unlikely.…”

Section: Discussionmentioning

confidence: 99%

Human Osteoarthritic Chondrocytes Possess an Increased Number of Insulin‐Like Growth Factor 1 Binding Sites but are Unresponsive to its Stimulation

Doré

Pelletier

DiBattista

et al. 1994

Arthritis & Rheumatism

186

117

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Objective. To characterize the insulin-like growth factor 1 (IGF-1) receptor in human osteoarthritic (OA) and normal adult chondrocytes. The biologic response of chondrocytes to IGF-1 stimulation was examined, as was the presence and synthesis of IGF binding proteins (IGFBP) in these cells.Methods. Binding studies, Northern blot, immunohistochemical analysis, and affinity cross-linking experiments were performed for characterization of the IGF receptor, and the latter method was also used for IGFBP determination. The biologic response was estimated via the incorporation of radiolabeled proline into a newly synthesized protein.Results histochemical studies with a monoclonal antibody (MAb) against the type 1 IGF receptor (aIR3) showed increased staining in OA cartilage compared with normal tissue. Biologic responses of chondrocytes after IGF-1 stimulation revealed that OA chondrocytes were unresponsive, whereas a 2.5-fold increase in new protein synthesis was observed in normal cells. Competition studies in normal chondrocytes revealed that both IGF-1 and IGF-2 displaced radiolabeled IGF-1 in a comparable manner; however, insulin at high concentration weakly competes. Moreover, MAb aIR3 effectively blocked specific binding in normal chondrocytes (77 %), but not in OA chondrocytes (26%). Northern blot and covalent cross-linking analyses revealed the specific band characteristic of type 1 receptor. With the latter technique, other bands corresponding to the IGFBPs were also detected. Comparison between normal and OA chondrocytes showed increased intensity of the IGFBP bands, particularly those corresponding to the IGFBP-3 doublet.Conclusion. It is shown that type 1 IGF receptor is expressed in human articular cartilage and that the level of binding sites is significantly increased in OA chondrocytes. Interestingly, despite the higher level of binding sites in OA cells, no response to IGF-1 stimulation was found in these cells. Our data suggest that this increase in specific binding may involve not only the type 1 IGF receptor but also IGFBP on the cell surface. The latter, by binding the IGF-1, will diminish the bioavailability of IGF-1 and thus prevent its anabolic action.Osteoarthritis (OA) is the most common of the various arthritic disorders affecting humans. The dis-

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Somatomedin activity in synovial fluid from patients with joint diseases.

Cited by 21 publications

References 32 publications

Mitogenic effects of hydroxyapatite and calcium pyrophosphate dihydrate crystals on cultured mammalian cells

Mitogenic effects of hydroxyapatite and calcium pyrophosphate dihydrate crystals on cultured mammalian cells

Elevated levels of insulin-like growth factor (IGF) binding protein-3 in rheumatoid arthritis synovial fluid inhibit stimulation by IGF-I of articular chondrocyte proteoglycan synthesis

Human Osteoarthritic Chondrocytes Possess an Increased Number of Insulin‐Like Growth Factor 1 Binding Sites but are Unresponsive to its Stimulation

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