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Differentiation

ISSN: 0301-4681 (printed version) ISSN: 1432-0436 (electronic version) Table of Contents Abstract Volume 55 Issue 2 (1994) pp 153-163

Effects of transforming growth factor beta (TGF<beta>) and 1,25 dihydroxyvitamin D3 on the function, cytochemistry and morphology of normal human osteoblast-like cells
Ronald T. Ingram, Susan K. Bonde, B. LawrenceRiggs, Lorraine A. Fitzpatrick Division of Endocrinology, Department of Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA Accepted in revised form August 19, 1993 Abstract. Individually, transforming growth factor beta (TGF<beta>) and 1,25dihydroxyvitamin D3 (1,25(OH)2D3) alter the growth and differentiation of normal and transformed osteoblast-like (OB) cells. Although recent evidence suggests interactions between TGF<beta> and 1,25(OH)2D3 may occur, little is known of the individual or combined effects of these hormones on the expression of the osteoblast phenotype at the cytochemical and biochemical levels in normal human OB (hOB) cells. Primary cultures of hOBs were treated with TGF<beta> (0.001- 10 ng/ml) and 1,25(OH)2D3 (0.1 pM-100 nM) either alone or in combination. TGF<beta> and 1,25(OH)2D3 stimulated spindle-shaped cells to become stellate in appearance and increased the number of cytoplasmic processes. TGF<beta> increased 3H-thymidine incorporation and 1,25(OH)2D3 reduced this effect. Conversely, procollagen type-I synthesis and secretion were increased in a dose-dependent manner in the presence of TGF<beta> but were not significantly affected in the presence of 1,25(OH)2D3. TGF<beta> and 1,25(OH)2D3 each marginally increased alkaline phosphatase (ALP) activity, but the combination synergistically increased ALP activity in a dose- and time-dependent manner at the cytochemical and biochemical level (three to tenfold over vehicle controls; n=12). In contrast, TGF<beta> reduced 1,25(OH)2D3-stimulated osteocalcin secretion. These data suggest that TGF<beta> stimulates hOB cells to actively produce collagen matrix and proliferate. The combination of TGF<beta> and 1,25(OH)2D3 , however, produces a synergistic increase in ALP activity and maintenance of collagen synthesis. 1,25(OH)2D3 stimulation may induce cells to advance to an endstage where cell proliferation is reduced and osteocalcin expression is promoted. Interactions between TGF<beta> and 1,25(OH)2D3 may represent important steps in the regulation of osteoblast differentiation and matrix production.

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