Endocrine Abstracts

Gut hormones are gastro-entero-pancreatic hormones released during the normal physiological response to feeding/fasting. Adequate nutrient intake and normal gastrointestinal function are critical to bone health, which can be under constant repair and remodelling. Gut hormones may integrate a connection between food intake and bone turnover.

We studied the effects of five gut hormones, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptides 1 and 2 (GLP-1, GLP-2), ghrelin (GHR) and obestatin (OB) on three osteoblastic cell lines MG-63, TE-85, and Saos-2, which represent different stages of maturity. mRNA was isolated and reverse transcribed to investigate the expression of these gut hormones receptors. PCR was performed confirming the expression of GIP, GHR and OB receptors for the most mature cell line (Saos-2), whereas the less mature expressed all the receptors.

MG-63, TE-85 and Saos-2 cells were cultured in presence of the gut hormones (1–1000 pM). Alkaline phosphatase (ALP) was assayed in supernatants and cell viability was investigated in cell layers, using a peptide substrate (glycil–phenylalanyl–amino-fluorocoumarin) specific for a protease present in live cells, generating a fluorescence signal.

Saos-2 showed significant increased ALP production to GIP, GHR, and OB exposure (P<0.01). GHR and OB graphs showed an opposite effect. TE-85 cells demonstrated functional responses to GHR1000 pM (P<0.0001) increasing ALP. MG-63 did not show any significant difference in ALP. Saos-2 viability was significantly decreased (P=0.048) for OB. TE-85 viability was significantly higher to GLP-1 100 pM stimulation (P=0.05), GLP-2 1 pM (P=0.04), OB 1 pM (P=0.03), and GHR 100 and 1000 pM (P=0.037, P=0.05, respectively). MG-63 viability was increased with GLP-1 100 pM (P=0.01), and GLP-2 1 pM (P=0.001).

These data reinforce the hypothesis that osteoblast function might be under the influence of gut hormones released in response to changes in dietary intake. These findings are relevant to the management of the secondary causes of bone disease associated with inadequate nutrition.