Curcumin suppresses increased bone resorption by inhibiting osteoclastogenesis in rats with streptozotocin-induced diabetes

Eur J Pharmacol. 2009 Oct 25;621(1-3):1-9. doi: 10.1016/j.ejphar.2009.08.025. Epub 2009 Aug 21.

Abstract

Curcumin is a potent inhibitor of the transcription factor activator protein-1 which plays an essential role in osteoclastogenesis. However, the effects of curcumin on bone metabolism have not been clarified in vivo. We reported herein the inhibitory effects of curcumin on the stimulated osteoclastic activity in insulin-dependent diabetes mellitus using rats with streptozotocin-induced diabetes. A dietary supplement of curcumin reversed the increase in levels of activity and mRNA of tartrate-resistant acid phosphatase (TRAP) and cathepsin K to control values. A histochemical analysis showed that the increase in TRAP-positive cells in the distal femur of the diabetic rats was reduced to the control level by the supplement. These results suggested that curcumin reduced diabetes-stimulated bone resorptive activity and the number of osteoclasts. When bone marrow cells were cultured with macrophage colony stimulating factor and receptor activator NF-kappaB ligand (RANKL), the increased activity to form TRAP-positive multinucleated cells and the increased levels of mRNA and protein of c-fos and c-jun in the cultured cells from diabetic rats decreased to control levels in the curcumin-supplemented rats. Similarly, the increased expression of c-fos and c-jun in the distal femur of the diabetic rats was significantly reduced by the supplement. These results suggested that curcumin suppressed the increased bone resorptive activity through the prevention of osteoclastogenesis associated with inhibition of the expression of c-fos and c-jun in the diabetic rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / genetics
  • Acid Phosphatase / metabolism
  • Amino Acids / urine
  • Animals
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / pathology
  • Bone Resorption / complications
  • Bone Resorption / drug therapy*
  • Bone Resorption / physiopathology
  • Calcium / metabolism
  • Cathepsin K / genetics
  • Cathepsin K / metabolism
  • Cell Differentiation / drug effects
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use*
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology*
  • Dietary Supplements
  • Eating / drug effects
  • Female
  • Femur / drug effects
  • Femur / metabolism
  • Femur / pathology
  • Femur / physiopathology
  • Glycosuria / complications
  • Glycosuria / drug therapy
  • Hydroxyproline / blood
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Osteocalcin / metabolism
  • Osteoclasts / cytology*
  • Osteoclasts / drug effects*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Staining and Labeling
  • Stem Cells / metabolism
  • Streptozocin
  • Tartrate-Resistant Acid Phosphatase

Substances

  • Amino Acids
  • Blood Glucose
  • Isoenzymes
  • RNA, Messenger
  • Osteocalcin
  • Streptozocin
  • deoxypyridinoline
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
  • Cathepsin K
  • Curcumin
  • Hydroxyproline
  • Calcium