The natural polyamines spermidine and spermine prevent bone loss through preferential disruption of osteoclastic activation in ovariectomized mice

• Published in: British journal of pharmacology Vol. 166; no. 3; pp. 1084 - 1096
• Main Authors: Yamamoto, Tomomi, Hinoi, Eiichi, Fujita, Hiroyuki, Iezaki, Takashi, Takahata, Yoshifumi, Takamori, Misa, Yoneda, Yukio
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2012; Nature Publishing Group
• Subjects: Administration, Oral; Animals; Biological and medical sciences; Blotting, Western; bone resorption; Bone Resorption - pathology; Bone Resorption - prevention & control; Cell Differentiation - drug effects; Cell Survival - drug effects; Cells, Cultured; Diseases of the osteoarticular system; Dose-Response Relationship, Drug; Female; Medical research; Medical sciences; Mice; Mice, Inbred Strains; NF-kappa B - genetics; NF‐κB; osteoblast; osteoclast; Osteoclasts - drug effects; Osteoclasts - pathology; osteoporosis; Osteoporosis - pathology; Osteoporosis - prevention & control; Osteoporosis. Osteomalacia. Paget disease; Ovariectomy; Pharmacology. Drug treatments; polyamine; Polyamines; p‐65; RANK Ligand - pharmacology; Research Papers; spermidine; Spermidine - administration & dosage; Spermidine - therapeutic use; spermine; Spermine - administration & dosage; Spermine - therapeutic use; Transcription, Genetic; Polyamine; Ovariectomy; Diseases of the osteoarticular system; Rodentia; bone resorption; Resorption; Osteoclast; p-65; Osteoarticular system; Osteoporosis; NF-κB; Vertebrata; Mammalia; Spermine; Mouse; Animal; Spermidine; Osteoblast; Bone defect; Transcription factor NFκB; Bone; Osteopenia
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.2012.01856.x

BACKGROUND AND PURPOSE Although naturally occurring polyamines are indispensable for a variety of cellular events in eukaryotic cells, little attention has been paid to their physiological and pathological significance in bone remodelling to date. In this study, we evaluated the pharmacological properties of several natural polyamines on the functionality and integrity of bone in both in vitro and in vivo experiments. EXPERIMENTAL APPROACH Mice were subjected to ovariectomy (OVX) and subsequent oral supplementation with either spermidine or spermine for determination of the bone volume together with different parameters regarding bone formation and resorption by histomorphometric analyses in vivo. Pre‐osteoclasts were cultured with receptor activator of NF‐κB ligand (RANKL), with or without spermidine and spermine to determine cellular maturation by tartrate‐resistant acid phosphatase (TRAP) staining and cellular viability by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide reduction in vitro. KEY RESULTS Spermidine or spermine, given in drinking water for 28 days, significantly prevented the increased osteoclast surface/bone surface ratio and the reduced bone volume following OVX in mice. Either spermidine or spermine significantly inhibited the increased number of multinucleated TRAP‐positive cells in osteoclasts cultured with RANKL in a concentration‐dependent manner without affecting cell survival. CONCLUSIONS AND IMPLICATIONS The natural polyamines spermidine and spermine prevented OVX‐induced bone loss through the disruption of differentiation and maturation of osteoclasts, rather than affecting osteoblasts. The supplementation with these natural polyamines could be beneficial for the prophylaxis as well as therapy of metabolic bone diseases such as post‐menopausal osteoporosis.