Effect of recombinant human growth hormone (rhGH) on the expression of NHE1 and AE2 membrane transporters on ex vivo bone growth in a rat model

Longitudinal growth of bones occurs through endochondral ossification within the epiphyseal growth plate (GP) of the skeleton. The effect of growth hormone (GH) on the expression of the membrane sodium hydrogen exchanger (NHE1) and anion exchanger (AE2) during skeletal growth was investigated using an ex-vivo model of rat bones. Tibia and metatarsal bones from day 10 pups were used for the investigation. The bones showed a steady rate of growth in the DMSO control media after 48 hours of incubation. The addition of recombinant human growth hormone (rhGH) to the culture media resulted in a direct stimulation of the whole bone growth, the whole growth plate length, and the whole growth plate density of chondrocytes. No significant changes (P>0.05) between the DMSO control and rhGH-treated were noted. Incorporation of membrane inhibitors (NHE1 and AE2) (5-(N-ethyl-N-isoprophyl) amiloride [EIPA] and (4,4-diiodothiocyano-2,2-stilbenedisulphonate) [DIDS] respectively in the culture media in the presence of rhGH remarkably suppressed the whole bone growth, whole GP length, GP chondrocytes population, and tissue expression of NHE1 (Na+ /H+ antiporter) and AE2 (HCO-3 anion exchanger) along the GP. Using NHE1 and AE2 rabbit polyclonal antibodies, tissue expression of Na+ /H+ antiporter and AE2 HCO-3 anion exchangers were significantly higher in rhGH than DMSO control cultured bones. The hormonal treatment appeared not to have direct stimulating effects on the growth of the bone, but may have an indirect metabolic effect that enhances chondrocyte proliferation and differentiation. EIPA and DIDS Plasma membrane inhibitors can still suppress longitudinal bone growth in the presence of rhGH.

Text 125578.pdf - Published Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (744kB) Official URL or Download Paper: https://www.ijagbio.com/pdf-files/25-156.pdf

Actions (login required)

View Item