Although cells of the osteoblast lineage express functional ERs, direct effects of estrogen on bone formation remain obscure. In the present study, we have investigated estrogen effects on osteoblastic and adipocytic differentiation from a mouse bone marrow stromal cell line, ST-2, which had been manipulated to overexpress either human ER alpha (ST2ER alpha) or ER beta (ST2ER beta). Treatment with bone morphogenetic protein-2 increased alkaline phosphatase activity as well as the number of Oil Red O-positive adipocytes, indicating that bone morphogenetic protein-2 stimulated both osteoblastic and adipocytic differentiation from these bipotential cells. In both ST2ER alpha and ST2ER beta cells, cotreatment with E2 caused enhancement of alkaline phosphatase activity and suppression of lipid accumulation. These effects were completely reversed by an ER antagonist, ICI182780. Therefore, the estrogen regulation occurred in an ER-specific manner but without ER subtype specificity. Moreover, dose response curves of the opposing effects of estrogen on osteoblastogenesis and adipogenesis formed an apparent mirror image, consistent with a reciprocal regulation of differentiation into the two cell lineages. These results demonstrate that estrogen directly modulates differentiation of bipotential stromal cells into the osteoblast and adipocyte lineages, causing a lineage shift toward the osteoblast. Such effects would lead to direct stimulation of bone formation and thereby contribute to the protective effects of estrogen on bone.

Abstract. Adiponectin is an anti-diabetic and anti-atherogenic adipokine that serves as a major determinant of insulin sensitivity. Thiazolidine derivatives increase circulating adiponectin, particularly the high molecular weight isoform, which has been shown to well correlate with amelioration of insulin resistance by thiazolidines in diabetic patients. α-glucosidase inhibitors are another class of anti-diabetic agents that specifically reduce postprandial blood glucose elevations, but its effect on adiponectin is largely unknown. In the present study we investigated effect of an α-glucosidase inhibitor, acarbose, together with pioglitazone, the only thiazolidine derivative available in Japan, on serum concentrations of adiponectin. Seventeen patients with type 2 diabetes were treated with acarbose and sixteen with pioglitazone for three months. Treatment with acarbose and pioglitazone decreased HbA1c values by 0.49% and 0.63%, respectively. Pioglitazone, as expected, increased serum levels of total adiponectin by 2.1 fold and its high molecular weight isoform by 3.6 fold. We found that acarbose also caused a small but significant increase in serum concentrations of total adiponectin. However, in contrast to pioglitazone, no appreciable changes were observed in the levels of high molecular weight adiponectin. In conclusion, acarbose increases serum concentrations of total adiponectin without preference of the high molecular weight isoform in type 2 diabetic patients. Clinical relevance of the increased adiponectin to the acarbose effects remains to be elucidated.

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