The Molecule Mechanism Of Bone Injuries Induced By Aluminum Exposure In Rats

The molecule mechanism of bone injuries induced by aluminum(Al) exposure in rats was studied. Wistar rats (n=100) were divided randomly into two groups. Experimental rats were given drinking water containing aluminum chloride (AlCl3, 430 mg Al3+/L), and control rats were given distilled water for up to 150 days. Ten rats were sacrificed in each group every 30 days. The levels of Al, calcium (Ca), phosphorus (P), magnesium (Mg), zinc (Zn), iron (Fe), copper (Cu), manganese (Mn), selenium (Se), boron (B) and strontium (Sr) in serum, bone and cartilage were measured. The serum levels of parathyroid hormone (PTH), calcitonin (CT) and osteocalcin (BGP) were detected using 125I radioimmunoassay (RIA) kits. The serum levels of 1, 25-dihydroxyvitaminD3 (1,25-(OH)2-D3), bone alkaline phosphatase(B-ALP), tartrate-resistantacid phosphatase-5b (TRACP-5b), carboxyterminal propeptide of type I procollagen (PICP), C-telopeptide of type I collagen (CTX-Ⅰ), collagenⅡand C-telopeptide of typeⅡcollagen (CTX-Ⅱ) and aggrecan were detected by solid phase sandwich ELISA. The mRNA expression of TGF-β1 and BMP-2 were detected by real-time Q-PCR. The histomorphology of bone and cartilage and ultrastructure of osteocyte and chondrocyte were observed. The results were shown as follows.1 The LD50 of AlCl3·6H2O on rats was 1283.60 mg/kg, and the Al exposure model was established successfully in rats on 430mg/L (Al3+).2 Under optical microscope, much cartilage-like immature matrix was discovered in the bone, and bone resorption was enhanced on days 120~150. The structure of cartilage matrix was loose and the number of chondrocyte was decreased. under electron microscope, the number of organelle and cytoplasmic electronic density decreased, nucleus pyknosed, and mitochondrion mitochondrion crista fractured. Rough endoplasmic reticulum was dilatated and its pellets dropped with the increase of the Al exposure time, and membranaceous structures exhibited vacuolar degeneration. The numbers of organelles and lipid drops decreased in chondrocyte, and matrix fiber became short and disordered with the increase of the Al exposure time.3 The serum levels of PTH, CT and 1,25-(OH)2-D3 were significantly lower in the Al-treated rats than in the control ones from days 90 (P<0.01), 30 (P<0.05) and 90 (P<0.01), respectively,which show that long-term Al exposure can indirectly inference with bone metabolism acting on hormoral regulation pathway.4 Al-treated rats showed lower deposition of Ca, Mg, P, Zn, Fe, Cu, Mn, B, Sr and Se compared with control ones. This indicates that Al exposure inhibits the deposition of mineralization elements. 5 The serum levels of BGP, B-ALP and PICP were significantly lower in the Al-treated rats than in the control ones from days 60 (P<0.05), 60 (P<0.01) and 90 (P<0.01), respectively. The mRNA expression of TGF-β1 and BMP-2 were significantly lower in the Al-treated rats than in the control ones from days 90 (P<0.01) and 60 (P<0.01), respectively. These findings suggest that long-term Al exposure inhibits the osteoblasts activity, metabolic enzymes activity and local regulating factor expression. As a result, bone formation was inhibited.6 Al-treated rats showed significantly higher serum levels of CTX-Ⅰcompared with control rats from day 90 (P<0.01), and lower serum levels of TRACP-5b on days 30, 60 and 150 (P<0.05) while the levels were reversed on day 120. These findings indicate that long-term Al exposure can induce bone injuries by increasing compensatory bone resorption.7 There are no statistical significance between Al-treated rats and control ones in the BMD of whole femurs and tibias. However, the BMD of femoral metaphysis and lumber (L4~L6) were significantly lower in the Al-treated rats than in the control ones on days 120~150 and 150 (both P<0.05), respectively. This indicates that long-term Al exposure can induce bone lose.8 The serum levels of collagenⅡwere significantly lower in the Al-treated rats than in the control ones from day 30 (P<0.05). The serum CTX-Ⅱand aggrecan levels were significantly higher in the Al-treated rats than in the control ones on day 90~150 (P<0.01) and 90~120 (P<0.05), respectively. These findings indicate that Al exposure can inhibit chondrocyte activity and the synthesis of collagenstroma, enhance collagenstroma degradation after 90 days of Al exposure, and then result in cartilage injuries.