Osteoblast modulators

Lisignoli G, Toneguzzi S, Grassi F, et al. Different chemokines are expressed in human arthritic bone biopsies IFN-gamma and IL-6 differently modulate IL-8, MCP-1 and rantes production by arthritic osteoblasts. Cytokine 2002 20(5) 231-238. 

Long GJ, Rosen JF. 1994. Lead perturbs 1,25 dihydroxyvitamin D3 modulation of intracellular calcium metabolism in clonal rat osteoblastic (ros 17/2.8) cells. Life Sci 54(19) 1395-1402. 

Zanello, L. P. and Norman, A. W. Rapid modulation of osteoblast ion channel responses by loc25(OH)2-vitamin D3 requires the presence of a functional vitamin D nuclear receptor. Proc. Natl Acad. Sci. USA 101 1589-1594,2004. 

Jilka RL, Weinstein RS, Bellido T, Parfitt AM, Manolagas SC (1998) Osteoblast programmed cell death (apoptosis) modulation by growth factors and cytokines. J Bone Miner Res 13 793-802... 

Taranta A, Brama M, Teti A, De 1, V, Scandurra R, Spera G, Agnusdei D, Termine JD, Migliaccio S (2002) The selective estrogen receptor modulator raloxifene regulates osteoclast and osteoblast activity in vitro. Bone 30 368-376... 

Tou L, Quibria N, Alexander JM (2001) Regulation ofhuman cbfal gene transcription in osteoblasts by selective estrogen receptor modulators (SERMs). Mol Cell Endocrinol 183 71-79... 

Nuttall ME, Stroup GB, Fisher PW, et al. (2000) Distinct mechanisms of action of selective estrogen receptor modulators in breast and osteoblastic cells. Am J Physiol Cell Physiol 279 C1550-C1557... 

Kozawa et al, 2000a and b). In both cell types, the p38 MAPK-specific inhibitor, SB203580, blocks SIP hsp27 induction and amplification of inositol phosphates, hi osteoblastic cells, PGE shmulates cyclic AMP formation and inhibits apoptosis. This appears to be mediated by a cyclic AMP-dependent modulation of SPHK and S IP production (Machwate etal., 1998)... 

The mechanism of action of the vitamin D metabolites remains under active investigation. However, calcitriol is well established as the most potent agent with respect to stimulation of intestinal calcium and phosphate transport and bone resorption. Calcitriol appears to act on the intestine both by induction of new protein synthesis (eg, calcium-binding protein and TRPV6, an intestinal calcium channel) and by modulation of calcium flux across the brush border and basolateral membranes by a means that does not require new protein synthesis. The molecular action of calcitriol on bone has received less attention. However, like PTH, calcitriol can induce RANK ligand in osteoblasts and proteins such as osteocalcin, which may regulate the mineralization process. The metabolites 25(OH)D and 24,25(OH)2D are far less... 

Very little work has been reported on the role of oxidative stress in osteoblasts. However, osteoblasts can be induced to produce intracellular ROS (Cortizo et al., 2000 Liu et al., 1999), which can cause a decrease in alkalinephosphatase (ALP) activity that is partially inhibited by vitamin E and cause cell death (Cortizo et al., 2000 Liu et al., 1999). Treatment of rat osteosarcoma ROS 17/2.8 cells with tumor necrosis factor-alpha (TNF-a) suppressed bone sialoprotein (BSP) gene transcription through a tyrosine kinase-dependent pathway that generates ROS (Samoto et al., 2002). H202 modulated intracellular calcium (Ca2+) activity in osteoblasts by increasing Ca2+ release from the intracellular Ca2+ stores (Nam et al., 2002). 

Lecanda, F., Towler, D.A., et.al.(1998) Gap junctional communication modulates gene expression in osteoblastic cells. Molecular Biology of the Cell 9 2249-58... 

Meazzini, M.C., Toma, C.D., et.al. (1998) Osteoblast cytoskeletal modulation in response to mechanical strain in vitro. Journal of Bone and Joint Surgery 16 170-180... 

Kessler and coworkers immobilized RGD peptides to a PMMA surface via a spacer incorporating an azobenzene unit [ 187]. The molecules were arranged in such a way that the RGD motifs were accessible to cells approaching the surface when the azo unit was in the E-form, and were hidden from the cells when the azo unit was in the Z-form. This enabled the reversible modulation of mouse osteoblast adhesion by irradiation with visible or UV light. However, the difference between on and off states is not very pronounced. Possibly, the accessibility of the RGD motif is not... 

Fig. 8. Schematic representation of protein-mediated cell adhesion on biomaterial surfaces. Biomaterial surface properties (such as hydrophilicity/hydrophobicity, topography, energy, and charge) affect subsequent interactions of adsorbed proteins these interactions include but are not limited to adsorbed protein type, concentration, and conformation. Changes in protein-surface interactions may alter accessibility of adhesive domains (such as the peptide sequence arginine-glycine-aspartic acid) to cells (such as osteoblasts, fibroblasts, or endothelial cells) and thus modulate cellular adhesion. (Adapted and redrawn from Schakenraad, 1996.)...

Schroder and co-workers (Schroder etal., 1999,2000) studied PolyP metabolism in bone tissues and osteblast cultures. They revealed that PolyP metabolism in human osteoblasts was modulated by stimulators of osteoblast proliferation and differentiation (Leyhausen et al., 1998). A combined treatment of the cells with dexamethasone, ft-glycerophosphate, epidermal growth factor (EGF), and ascorbic acid resulted in a dramatic decrease in PolyP content. This decrease is caused mainly by a decrease in the amount of soluble long-chain PolyPs. The amount of this PolyP fraction, but not the amount of insoluble long-chain PolyPs, further decreases after additional treatment of the cells with la, 25-dihydroxy vitamin D3. The decrease in PolyP content during treatment with dexamethasone, ft-glycerophosphate, EGF and ascorbic acid is accompanied by a decrease in exopolyphosphatase activity. However, additional treatment with la, 25-dihydroxyvitamin D3 results in a significant increase of the enzyme activity. Therefore, it is reasonable to assume that PolyP... 

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