Impaired gastric acidification negatively affects calcium homeostasis and bone mass.

TY - JOUR

T1 - Impaired gastric acidification negatively affects calcium homeostasis and bone mass.

AU - Schinke, Thorsten

AU - Schilling, Arndt

AU - Baranowsky, Anke

AU - Seitz, Sebastian

AU - Marshall, Robert P

AU - Linn, Tilman

AU - Bläker, Michael

AU - Huebner, Antje K

AU - Schulz, Ansgar

AU - Simon, Ronald

AU - Gebauer, Matthias

AU - Priemel, Matthias

AU - Kornak, Uwe

AU - Perkovic, Sandra

AU - Barvencik, Florian

AU - Beil, F Timo

AU - Andrea, Del Fattore

AU - Frattini, Annalisa

AU - Streichert, Thomas

AU - Püschel, Klaus

AU - Villa, Anna

AU - Debatin, Klaus-Michael

AU - Rueger, Johannes Maria

AU - Teti, Anna

AU - Zustin, Jozef

AU - Sauter, Guido

AU - Amling, Michael

PY - 2009

Y1 - 2009

N2 - Activation of osteoclasts and their acidification-dependent resorption of bone is thought to maintain proper serum calcium levels. Here we show that osteoclast dysfunction alone does not generally affect calcium homeostasis. Indeed, mice deficient in Src, encoding a tyrosine kinase critical for osteoclast activity, show signs of osteopetrosis, but without hypocalcemia or defects in bone mineralization. Mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells, have the expected defects in gastric acidification but also secondary hyperparathyroidism and osteoporosis and modest hypocalcemia. These results suggest that alterations in calcium homeostasis can be driven by defects in gastric acidification, especially given that calcium gluconate supplementation fully rescues the phenotype of the Cckbr-mutant mice. Finally, mice deficient in Tcirg1, encoding a subunit of the vacuolar proton pump specifically expressed in both osteoclasts and parietal cells, show hypocalcemia and osteopetrorickets. Although neither Src- nor Cckbr-deficient mice have this latter phenotype, the combined deficiency of both genes results in osteopetrorickets. Thus, we find that osteopetrosis and osteopetrorickets are distinct phenotypes, depending on the site or sites of defective acidification.

AB - Activation of osteoclasts and their acidification-dependent resorption of bone is thought to maintain proper serum calcium levels. Here we show that osteoclast dysfunction alone does not generally affect calcium homeostasis. Indeed, mice deficient in Src, encoding a tyrosine kinase critical for osteoclast activity, show signs of osteopetrosis, but without hypocalcemia or defects in bone mineralization. Mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells, have the expected defects in gastric acidification but also secondary hyperparathyroidism and osteoporosis and modest hypocalcemia. These results suggest that alterations in calcium homeostasis can be driven by defects in gastric acidification, especially given that calcium gluconate supplementation fully rescues the phenotype of the Cckbr-mutant mice. Finally, mice deficient in Tcirg1, encoding a subunit of the vacuolar proton pump specifically expressed in both osteoclasts and parietal cells, show hypocalcemia and osteopetrorickets. Although neither Src- nor Cckbr-deficient mice have this latter phenotype, the combined deficiency of both genes results in osteopetrorickets. Thus, we find that osteopetrosis and osteopetrorickets are distinct phenotypes, depending on the site or sites of defective acidification.

M3 - SCORING: Zeitschriftenaufsatz

VL - 15

SP - 674

EP - 681

JO - NAT MED

JF - NAT MED

SN - 1078-8956

IS - 6

M1 - 6

ER -