Alendronate inhibits osteopontin expression enhanced by parathyroid hormone-related peptide (PTHrP) in the rat kidney.
It has been reported that osteopontin (OPN) plays an important role during urolithiasis as well as bone formation. Generation of stones in the urinary tract may be associated with osteoporosis and bisphosphonates are potent inhibitors of bone resorption, being used with effect in the management of bone disease. We therefore investigated the relationship between alendronate, a bisphosphonate derivative, and OPN expression in the kidney. Alendronate was administered to rats made hypercalcemic by treatment with parathyroid hormone-related peptide (PTHrP). The renal expression of OPN was then evaluated at both protein and mRNA levels. OPN expression was enhanced in the distal tubular cells of hypercalcemic rats and was decreased by alendronate. The observed inhibition of OPN expression suggests an ability of alendronate and other bisphosphonates to act as inhibitors of stone formation in the urinary tract.
Yasui
T
T
Department of Urology, Nagoya City University Medical School, Nagoya, Japan.
Fujita
K
K
Sasaki
S
S
Iguchi
M
M
Hirota
S
S
Nomura
S
S
Azuma
Y
Y
Ohta
T
T
Kohri
K
K
D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D004164:Diphosphonates / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006934:Hypercalcemia / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D053495:Osteopontin; D010281:Parathyroid Hormone / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein; D010750:Phosphoproteins / Q000235:genetics; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000032:analysis / Q000235:genetics*; D014545:Urinary Calculi / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control
D004164:Diphosphonates; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; D019386:Alendronate