Endocrine Abstracts

Adiponectin, the most abundant peptide hormone secreted from adipose tissue, has been negatively correlated with obesity and can induce varying responses on bone. There are significant discrepancies in the published data, showing increased, decreased or no effects on bone turnover.

We investigated the effects of adiponectin on the human osteosarcoma cell line Saos-2. After culture with varying concentrations of adiponectin (10–100 nM), supernatants were collected to measure alkaline phosphatase (ALP) and osteocalcin. These detected a significant decrease in ALP in a negative-dose mode (P=0.003). Osteocalcin did not show any significant difference. Cell viability was significantly higher (P=0.001) and directly correlated with increasing adiponectin concentrations (P<0.001).

mRNA was extracted and reverse transcribed to analyse ALP and glycosylphosphatidylinositol specific phospholipase-D1 (GPLD1) relative expression, using quantitative real time PCR. GPLD1 was investigated as a probable enzyme causing ALP detachment from the plasma membrane. The relative expression showed opposite behaviour: higher ALP and lower GPLD1 with increasing adiponectin.

A Saos-2 strain, stably transfected with a c-fos-driven reporter gene, was used to investigate c-fos induction in presence of adiponectin and/or ATP. The data showed significantly higher (P<0.05) induction when adiponectin and ATP were both present.

These data may explain some of the contrasting findings of adiponectin at the cellular level. No significant difference in osteocalcin secretion was demonstrated but although ALP expression is elevated its release from cells is decreased due perhaps to the low levels of GPLD1.

c-fos (a proto-oncogene implicated in bone remodelling) activation was synergistically induced by adiponectin in the presence of ATP, greater than with adiponectin or ATP on their own, suggesting that ATP could enhance the sensitivity of bone cells targeting the sites where bone remodelling is required.

These data confirm the contradictory findings that are observed in reported studies, suggesting that intracellular/local controlling factors should be further investigated.