Aluminum action on mouse bone cell metabolism and response to PTH and 1,25(OH)2D3.
Aluminum (Al) accumulation in bone is associated with low bone formation and mineralization rates; resorption may also be reduced. The mechanism of these Al-induced changes was investigated using cultured mouse osteoblast-like (OB) and osteoclast-like (OC) cells. The Al effect on bone resorption was measured by the in vitro release of 45Ca and beta-glucuronidase from mouse fetal limb-bones. Al had a biphasic effect. High concentrations (greater than 1.5 X 10(-6) M) of Al inhibited collagen and DNA synthesis, ornithine decarboxylase and alkaline phosphatase activity in OB, and depressed tartrate-resistant acid phosphatase activity in OC. Lower Al concentrations stimulated these cellular activities and 45Ca and beta-glucuronidase release from fetal bones. Al had no effect on basal cAMP levels in OB but inhibited the stimulating effect of bPTH on cAMP content. Al also altered the 1,25(OH)2D3 effects on the ornithine decarboxylase activity of OB cells. These data suggest that: (i) the low bone formation observed in vivo during Al intoxication may be due to the inhibition of collagen synthesis and to depressed cell proliferation; and (ii) Al may indirectly influence bone remodeling by interfering with the actions of bPTH and 1,25(OH)2D3 on bone cells.
D000135:Acid Phosphatase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D001862:Bone Resorption / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D013644:Tartrates / Q000494:pharmacology
D010281:Parathyroid Hormone; D013644:Tartrates; D003094:Collagen; D004247:DNA; D000535:Aluminum; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D009955:Ornithine Decarboxylase; D002117:Calcitriol; C029768:tartaric acid