Effects of spermidine on bone microstructure of femurs of senile mice
SU Jingke1, SU Jinghua2, HAN Ning1, TIAN Xiaoyu3, DANG Ruijie3, FENG Jin3, GENG Yanqiu1
1. Department of Nephrology, 2. Health Medical Center, the Third Medical Center, PLA General Hospital, Beijing 100039,China; 3. Institute of Orthopedics, the First Medical Center, PLA General Hospital, Beijing 100853,China
Abstract:Objective To investigate the effects of spermidine on bone microstructure of femurs of senile mice. Methods Twenty 21-month-old C57 mice were randomly divided into the vehicle group (n=10 ) and spermidine group (3 mmol/L spermidine in drinking water, n=10). Body weight was measured weekly during the study. After 12 weeks of intervention, biochemical indexes of bone metabolism in serum and urine were tested and histomorphometry of femurs was measured by micro-CT (microcomputed tomography). Results Compared with the vehicle mice, spermidine had no effect on the weight of senile mice. Spermidine intervention significantly increased serum levels of ALP (P<0.05), elevated the trabecular bone volume per tissue volume (Tb.BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th)and bone mineral density (BMD), and reduced trabecular separation (Tb.Sp). Conclusions Spermidine attenuates age-associated osteoporosis in senile mice.
Goode S C, Beshears J L, Goode R D, et al. Putting the brakes on breaks: osteoporosis screening and fracture prevention[J]. Geriatr Orthop Surg Rehabil, 2017,8(4):238-243.
[6]
Ding Y, Jiang H, Meng B, et al. Sweroside-mediated mTORC1 hyperactivation in bone marrow mesenchymal stem cells promotes osteogenic differentiation[J]. J Cell Biochem, 2019,120(9):16025-16036.
[7]
Eisenberg T, Abdellatif M, Schroeder S, et al. Cardioprotection and lifespan extension by the natural polyamine spermidine[J]. Nat Med, 2016,22(12):1428-1438.
[8]
Tong D, Hill J A. Spermidine promotes cardioprotective autophagy[J]. Circ Res, 2017,120(8):1229-1231.
[9]
Gao M, Zhao W, Li C, et al. Spermidine ameliorates non-alcoholic fatty liver disease through regulating lipid metabolism via AMPK[J]. Biochem Biophys Res Commun, 2018,505(1):93-98.
[10]
Gupta V K, Scheunemann L, Eisenberg T, et al. Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner[J]. Nat Neurosci, 2013,16(10):1453-1460.
[11]
Madeo F, Bauer M A, Carmona G D, et al. Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans?[J]. Autophagy, 2019,15(1):165-168.
Liu W, Zhou L, Zhou C, et al. GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation[J]. Nat Commun, 2016,7:12794.
[15]
Yamamoto T, Hinoi E, Fujita H, et al. The natural polyamines spermidine and spermine prevent bone loss through preferential disruption of osteoclastic activation in ovariectomized mice[J]. Br J Pharmacol, 2012,166(3):1084-1096.
[16]
Yamada T, Park G, Node J, et al. Daily intake of polyamine-rich Saccharomyces cerevisiae S 631 prevents osteoclastic activation and bone loss in ovariectomized mice[J]. Food Sci Biotechnol, 2019,28(4):1241-1245.
[17]
Labouesse M A, Gertz E R, Piccolo B D, et al. Associations among endocrine, inflammatory, and bone markers, body composition and weight loss induced bone loss[J]. Bone, 2014,64:138-146.
[18]
Fogelholm G M, Sievánen H T, Kukkonen T K, et al. Bone mineral density during reduction, maintenance and regain of body weight in premenopausal, obese women[J]. Osteoporos Int, 2001,12(3):199-206.
Rokidi S, Paschalis E P, Klaushofer K, et al. Organic matrix quality discriminates between age and BMD-matched fracturing versus non-fracturing post-menopausal women: a pilot study[J]. Bone, 2019,127:207-214.
[21]
Ott S M. Cortical or trabecular bone: what's the difference?[J]. Am J Nephrol, 2018,47(6):373-375.
[22]
Khosla S, Hofbauer L C. Osteoporosis treatment: recent developments and ongoing challenges[J]. Lancet Diabetes Endocrinol, 2017,5(11):898-907.