Biomedical subjects

P Orcel

Publications and source records attributed to P Orcel.

45 records · Page 3Linked to original sources

PubMed1990

Effects of transforming growth factor-beta on long-term human cord blood monocyte cultures.

Transforming growth factor-beta (TGF-beta) modulates growth and differentiation in many cell types and is abundant in bone matrix. We recently showed that human cord blood monocytes cultured in the presence of 1,25(OH)2D3 acquire some features of osteoclast precursors. Since TGF-beta has been shown to influence bone resorption in organ culture, we have studied the effect of TGF-beta (1-1,000 pg/ml) on cord blood monocyte cultures. These cells were cultured on plastic substrate during 3 weeks in the presence of 20% horse serum and 10(-9) M 1,25(OH)2D3. TGF-beta, from a concentration of 10 pg/ml in the culture medium, decreased in a dose dependent manner the formation of multinucleated cells. At a concentration of TGF-beta of 1 ng/ml, the multinucleated cells were reduced to 2.1% +/- 0.3%, compared to 19.3% +/- 1.5% in control cultures. TGF-beta inhibited in a dose-dependent manner the proliferation of cord blood monocytes as assessed by 3H-thymidine incorporation at 7 and 14 days of culture. The fusion index was also decreased by 3 weeks of treatment with TGF-beta. Indomethacin did not reverse the inhibitory effects of TGF-beta. The expression of the osteoclastic phenotype was assessed using two different antibodies: 23C6, a monoclonal antibody directed against the vitronectin receptor, which is highly expressed by osteoclasts but not by adult monocytes, and an antibody to HLA-DR, which is not present on osteoclast. TGF-beta decreased the expression of HLA-DR and increased in a dose-dependent manner the proportion of 23C6-labeled cells; these results suggest that TGF-beta could modulate a differentiation effect to the osteoclastic phenotype. However, when cord blood monocytes were cultured on devitalized rat calvariae prelabeled with 45Ca, TGF-beta did not induce any 45Ca release from bone cultured with monocytes, suggesting that full osteoclastic differentiation was not achieved. These results emphasize the complex role of TGF-beta in the local regulation of bone cell differentiation and in bone remodeling.

Calcium Radioisotopes↗

PubMed1989

[Osteoclastic activation factors].

Explore the source record for details and available documents.

Bone Resorption↗

PubMed1989

Cyclosporin A induces in vivo inhibition of resorption and stimulation of formation in rat bone.

We investigated a possible "in vivo" effect of cyclosporin A, an immunosuppressive agent, on normal rat bone remodeling. At an oral daily dose of 7 mg/kg for 14 days, the blood level of cyclosporin A was in the usual effective range and no change in renal function or magnesium metabolism was observed. Treated rats had decreased bone resorption: urinary hydroxyproline, plasma acid phosphatase, and the number of osteoclasts in caudal vertebrae were significantly reduced. By contrast, bone formation assessed by dynamic histomorphometry after double tetracycline labeling was increased. No modification of calciotropic hormones (vitamin D metabolites and parathyroid hormone as assessed by urinary cyclic AMP) was observed at the end of the treatment. These results suggest that in vivo cyclosporin A treatment induces bone remodeling modifications related to either a direct or a lymphokine-mediated effect on bone cells.

Acid Phosphatase↗

PubMed1987

[Spontaneous fissures and fractures of the legs in patients with osteoporosis treated with sodium fluoride].

Thirteen cases of spontaneous fissure or fracture of the lower limbs observed in 8 patients under treatment with sodium fluoride are reported; 7 of these patients were being treated for osteoporosis. The fissures occurred after 20 months of treatment on average and were revealed by pain in the metaphysis with early high radionuclide uptake. Three to 4 weeks later, X-ray films showed a linear bone condensation area, involving in most cases, the tibial metaphysis, the femoral neck and the calcaneum. The prognosis was usually favourable, but 2 patients required surgery for fissure of the femoral neck with rupture of the cortex. Fluor seems to be responsible for the fissures which cannot be avoided by calcium and/or vitamin D intake. The main pathogenic hypotheses are excessive bone resorption, large amounts of poorly mineralized osteoid tissue and architectural abnormalities of the trabeculae. When such fissures occur, fluoride therapy must be discontinued and the limb put at rest, but since this side-effect is rare and usually benign the principle of a treatment that is beneficial in many cases of osteoporosis need not be revised.

Aged↗

PubMed1987