Comments on an article by M. Kassem and colleagues on the production and action of transforming growth factor (TGF)-beta in human osteoblast cultures. Recruitment and development of inducible osteoprogenitor cells; Im...
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Comments on an article by M. Kassem and colleagues on the production and action of transforming growth factor (TGF)-beta in human osteoblast cultures. Recruitment and development of inducible osteoprogenitor cells; Impact of TGF-beta; Definition of the crucial phases of osteoblastic development; Determination of optimal bone cell function by sequential gene expression.
Skeletal mass, both systemically and at sites of localized bone disease, is determined by the delicate balance that exists between bone formation and bone loss. Bone formation is performed by osteoblasts. These cells ...
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Skeletal mass, both systemically and at sites of localized bone disease, is determined by the delicate balance that exists between bone formation and bone loss. Bone formation is performed by osteoblasts. These cells secrete type I collagen and noncollagenous proteins of bone that form the bone matrix. Bone resorption is performed by osteoclasts. Osteoclasts resorb bone by forming an acidic extracellular compartment at their cell surface membrane–bone interface and by secreting cathepsin k into this compartment, with the end result being degradation of the bone matrix.
Previous studies have shown that the actions of IGF-II in bone are determined not only by its concentration, but also by the concentration of IGFBP-4 as well as other IGFBPs. In this study, we sought to determine by W...
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Previous studies have shown that the actions of IGF-II in bone are determined not only by its concentration, but also by the concentration of IGFBP-4 as well as other IGFBPs. In this study, we sought to determine by Western ligand blotting the effects of growth hormone, IGF-I and IGF-II on the production of IGFBP-3 and IGFBP-4 in TE89 human osteosarcoma cells and in untransformed normal human bone cells derived from rib. Human growth hormone at 10 mug/l decreased the amount of IGFBP-4 but had no effect on the IGFBP-3 level in the conditioned medium of low density cultures of TE89 cells and human bone cells derived from rib. Human growth hormone had no effect on IGFBP-3 or IGFBP-4 levels in the conditioned medium of high density human bone cell cultures. IGF-I and IGF-II, which increased human bone cell proliferation, decreased the level of IGFBP-4 (30% of control at 100 mug/IIGF-I and IGF-II) but increased the level of IGFBP-3 (3-10 fold at 100 mug/l IGF-I and IGF-II) after 48 h of treatment in the conditioned medium of both low and high density TE89 cell cultures. Similar changes in IGFBP-3 and IGFBP-4 levels were also seen in the conditioned medium of human bone cells derived from rib after treatment with IGF-I and IGF-II. Studies to determine the underlying molecular mechanisms by which IGF-II decreased the amount of IGFBP-4 in the conditioned medium revealed that IGF-II decreased the IGFBP-4 mRNA abundance and increased the IGFBP-3 mRNA abundance in human bone cells. Based on the above findings, we conclude that the production of both IGFBP-3 and IGFBP-4 is regulated in bone cells and that local and systemic agents may modulate the responsiveness of bone cells to IGFs by regulated secretion of IGFBP-3 and IGFBP-4.
We studied the influence of fasting serum from nine insulin-dependent diabetic children and adolescents under insufficient metabolic control on normal human bone cells in vitro compared with serum from eight sex- and ...
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We studied the influence of fasting serum from nine insulin-dependent diabetic children and adolescents under insufficient metabolic control on normal human bone cells in vitro compared with serum from eight sex- and age-matched controls. Cell number 24 h after plating was significantly less under diabetic serum, indicating impaired cell attachment, spreading and initiation of cell proliferation. Cell number after five days was reduced by 1% diabetic serum, while higher serum concentrations had diverging effects on osteoblast proliferation. Collagen synthesis of human osteoblasts was significantly reduced by 8% diabetic serum compared to 8% control serum, while synthesis of non-collagenous proteins was not affected. Duration of diabetes (several weeks up to 12 years) had no influence on these parameters. The serum from one patient, which was studied a second time under excellent metabolic control three months later, however, had lost its inhibitory influence on collagen synthesis of osteoblasts. The pattern of the interstitial collagen types I, III and V was not altered by diabetic serum. These results indicate that defective regulation of proliferation and collagen synthesis of osteoblasts by components present in human diabetic serum may be an important factor in the development of diabetic osteopenia. The negative influence might be explained in part by reduced levels of IGF-I and elevated levels of IGF binding protein-I in the diabetic sera.
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