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Critical Reviews™ in Eukaryotic Gene Expression
IF: 1.841 5-Year IF: 1.927 SJR: 0.649 SNIP: 0.516 CiteScore™: 1.96

ISSN Print: 1045-4403
ISSN Online: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukarGeneExpr.v11.i4.30
20 pages

Regulation of Osteoblast Growth by Interactions Between Transforming Growth Factor-b and 1a,25-Dihydroxyvitamin D3

Alper Gurlek
Mayo Clinic and Foundation, Departments of Nephrology, Biochemistry, and Molecular Biology, Rochester, MN
Rajiv Kumar
Mayo Clinic and Foundation, Departments of Nephrology, Biochemistry, and Molecular Biology, Rochester, MN

ABSTRACT

Osteoblast growth and differentiation encompass a series of events including proliferation, changes in cell shape, and expression of the markers specific for osteoblast phenotype. Both transforming growth factor-b (TGF-b) and 1a,25-dihydroxyvitamin D3 (1a,25[OH]2D3) are effective in regulating osteoblast proliferation, differentiation, bone matrix maturation and cell-specific gene expression. Although there is some degree of controversy regarding the influences on osteoblasts in vitro, it is generally agreed that TGF-b stimulates osteoblast proliferation and growth, and inhibits the expression of the markers characteristic of the osteoblast phenotype such as osteocalcin. In contrast, 1a,25(OH)2D3 causes inhibition of the proliferation of osteoblasts, arrests their growth, and stimulates expression of specific markers. In many studies, complex interactions have been demonstrated between TGF-b and 1a,25(OH)2D3 modulating their receptor expression, synthesis, and effects on osteoblast-specific gene expression. The cooperative actions of TGF-b and 1a,25(OH)2D3 can be synergistic or antagonistic. It has recently been established that Smad proteins that transduce signals downstream the TGF-b stimulation may mediate the crosstalk between TGF-b and 1a,25(OH)2D3 signaling. Future studies should focus on the explanation of the molecular basis of these interactions and the in vivo consequences of the regulation of osteoblast growth and differentiation by TGF-b and 1a,25(OH)2D3.