Increased cathepsin K and tartrate-resistant acid phosphatase expression in bone of streptozotocin-induced diabetic rats.
The effect of insulin-dependent diabetes mellitus (IDDM) on bone metabolism was evaluated using the streptozotocin (STZ)-induced diabetic rat 1 week after the induction of diabetes. The urinary excretion of cross-linked N-telopeptides of type I collagen (NTx) and deoxypyridinoline (Dpd) in diabetic rats increased to 3.6-fold and 1.2-fold the control level, respectively. The amount of hydroxyproline and calcium in the distal femur of diabetic rats significantly decreased to 76% and 90% of the control, respectively. The levels of serum osteocalcin and alkaline phosphatase (ALP) activity in the distal femur of the diabetic rats were significantly reduced to about 40% and 70% of the control levels, respectively. The decrease in the expression osteocalcin was observed in distal femur of the diabetic rats, although the level of ALP mRNA was unchanged. The activity and the mRNA level of tartrate-resistant acid phosphatase (TRAP) increased to 1.5- and 2.3-fold the control level, respectively, in distal femur of the diabetic rats. The activity, protein, and mRNA levels of cathepsin K of diabetic rats also elevated to about 2-, 2.3-, and 2-fold the control levels, respectively. These results suggest that IDDM contributes to bone loss through changes in gene expression of TRAP and cathepsin K in osteoclasts as well as osteocalcin in osteoblasts resulting in increased bone resorptive activity and decreased bone formation.
Hie
Mamiko
M
Department of Food Science and Nutrition, Nara Women's University, Nara 630, Japan.
Shimono
Masumi
M
Fujii
Kayoko
K
Tsukamoto
Ikuyo
I
D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000201:enzymology*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D015675:Osteocalcin / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase
D015415:Biomarkers; D007527:Isoenzymes; D012333:RNA, Messenger; D015675:Osteocalcin; D013311:Streptozocin; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002403:Cathepsins; D056657:Cathepsin K; C534133:Ctsk protein, rat; D005947:Glucose; D006909:Hydroxyproline; D002118:Calcium