Skip to main content

Omentin-1 exerts bone-sparing effect in ovariectomized mice

Abstract

Summary

Omentin-1 inhibited osteoblast differentiation in vitro. In co-culture systems of osteoblasts and osteoclast precursors, omentin-1 reduced osteoclast formation by stimulating osteoprotegerin (OPG) and inhibiting receptor activator for nuclear factor κB ligand (RANKL) production in osteoblasts. In vivo, adenovirus-mediated overexpression of omentin-1 suppressed bone turnover and restored bone mineral density (BMD) and bone strength in ovariectomized mice.

Introduction

Omentin-1 (also intelectin-1) is a recently identified visceral adipose tissue-derived cytokine that is highly abundant in plasma. This study was undertaken to investigate the effects of omentin-1 on bone metabolism.

Methods

Osteoblast differentiation was assessed by measuring alkaline phosphatase activity, osteocalcin production and matrix mineralization. OPG and RANKL protein expression and secretion in osteoblasts were detected by Western blot and ELISA, respectively. The effect of recombinant omentin-1 on osteoclast formation was examined in co-culture systems of osteoblasts and osteoclast precursors. The effects of intravenous administration of adenoviral-delivered omentin-1 on bone mass, bone strength, and bone turnover were also examined in ovariectomized mice.

Results

In vitro, omentin-1 inhibited osteoblast differentiation, while it had no direct effect on osteoclast differentiation; it also reduced osteoclast formation in the co-culture systems through stimulating OPG and inhibiting RANKL production in osteoblasts. In vivo, adenovirus-mediated overexpression of omentin-1 partially restored BMD and bone strength in ovariectomized mice, accompanied by decreased levels of plasma osteocalcin and tartrate-resistant acid phosphatase-5b and lower serum RANKL/OPG ratios.

Conclusion

The present study suggests that omentin-1 ameliorates bone loss induced by estrogen deficiency via downregulating the RANKL/OPG ratio.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. 1.

    Poulos SP, Hausman DB, Hausman GJ (2010) The development and endocrine functions of adipose tissue. Mol Cell Endocrinol 323:20–34

    Article  CAS  PubMed  Google Scholar 

  2. 2.

    Singla P, Bardoloi A, Parkash AA (2010) Metabolic effects of obesity: a review. World J Diabetes 1:76–88

    Article  PubMed  Google Scholar 

  3. 3.

    Holecki M, Wiecek A (2010) Relationship between body fat mass and bone metabolism. Pol Arch Med Wewn 120:361–367

    CAS  PubMed  Google Scholar 

  4. 4.

    Reid IR (2010) Fat and bone. Arch Biochem Biophys 503:20–27

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Williams GA, Wang Y, Callon KE, Watson M, Lin JM, Lam JB, Costa JL, Orpe A, Broom N, Naot D, Reid IR, Cornish J (2009) In vitro and in vivo effects of adiponectin on bone. Endocrinology 150:3603–3610

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    Ealey KN, Kaludjerovic J, Archer MC, Ward WE (2008) Adiponectin is a negative regulator of bone mineral and bone strength in growing mice. Exp Biol Med (Maywood) 233:1546–1553

    Article  CAS  Google Scholar 

  7. 7.

    Bartell SM, Rayalam S, Ambati S, Gaddam DR, Hartzell DL, Hamrick M, She JX, Della-Fera MA, Baile CA (2011) Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob/ob mice. J Bone Miner Res. doi:10.1002/jbmr.406

  8. 8.

    Hamrick MW, Della-Fera MA, Choi YH, Pennington C, Hartzell D, Baile CA (2005) Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice. J Bone Miner Res 20:994–1001

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Berner HS, Lyngstadaas SP, Spahr A, Monjo M, Thommesen L, Drevon CA, Syversen U, Reseland JE (2004) Adiponectin and its receptors are expressed in bone-forming cells. Bone 35:842–849

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    Kralisch S, Klein J, Bluher M, Paschke R, Stumvoll M, Fasshauer M (2005) Therapeutic perspectives of adipocytokines. Expert Opin Pharmacother 6:863–872

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Schaffler A, Neumeier M, Herfarth H, Furst A, Scholmerich J, Buchler C (2005) Genomic structure of human omentin, a new adipocytokine expressed in omental adipose tissue. Biochim Biophys Acta 1732:96–102

    CAS  PubMed  Google Scholar 

  12. 12.

    Yang RZ, Lee MJ, Hu H, Pray J, Wu HB, Hansen BC, Shuldiner AR, Fried SK, McLenithan JC, Gong DW (2006) Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. Am J Physiol Endocrinol Metab 290:E1253–E1261

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Komiya T, Tanigawa Y, Hirohashi S (1998) Cloning of the novel gene intelectin, which is expressed in intestinal Paneth cells in mice. Biochem Biophys Res Commun 251:759–762

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    de Souza Batista CM, Yang RZ, Lee MJ et al (2007) Omentin plasma levels and gene expression are decreased in obesity. Diabetes 56:1655–1661

    Article  PubMed  Google Scholar 

  15. 15.

    Moreno-Navarrete JM, Catalán V, Ortega F, Gómez-Ambrosi J, Ricart W, Frühbeck G, Fernández-Real JM (2010) Circulating omentin concentration increases after weight loss. Nutr Metab (Lond) 7:27

    Article  Google Scholar 

  16. 16.

    Tan BK, Pua S, Syed F, Lewandowski KC, O’Hare JP, Randeva HS (2008) Decreased plasma omentin-1 levels in type 1 diabetes mellitus. Diabet Med 25:1254–1255

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    Pan HY, Guo L, Li Q (2010) Changes of serum omentin-1 levels in normal subjects and in patients with impaired glucose regulation and with newly diagnosed and untreated type 2 diabetes. Diabetes Res Clin Pract 88:29–33

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    Yamawaki H, Tsubaki N, Mukohda M, Okada M, Hara Y (2010) Omentin, a novel adipokine, induces vasodilation in rat isolated blood vessels. Biochem Biophys Res Commun 393:668–672

    Article  CAS  PubMed  Google Scholar 

  19. 19.

    Yamawaki H, Kuramoto J, Kameshima S, Usui T, Okada M, Hara Y (2011) Omentin, a novel adipocytokine inhibits TNF-induced vascular inflammation in human endothelial cells. Biochem Biophys Res Commun 408:339–343

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    Duan XY, Xie PL, Ma YL, Tang SY (2010) Omentin inhibits osteoblastic differentiation of calcifying vascular smooth muscle cells through the PI3K/Akt pathway. Amino Acids. doi:10.1007/s00726-010-0800-3

  21. 21.

    Luo XH, Guo LJ, Xie H, Yuan LQ, Wu XP, Zhou HD, Liao EY (2006) Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts through the MAPK signaling pathway. J Bone Miner Res 21:1648–1656

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Xie H, Sun M, Liao XB et al (2010) Estrogen receptor α36 mediates a bone-sparing effect of 17β-estrodiol in postmenopausal women. J Bone Miner Res 26:156–168

    Article  Google Scholar 

  23. 23.

    Li H, Xie H, Liu W, Hu R, Huang B, Tan YF, Liao EY, Xu K, Sheng ZF, Zhou HD, Wu XP, Luo XH (2009) A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans. J Clin Invest 119:3666–3677

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Liu J, Xu K, Wen G, Guo H, Li S, Wu X, Dai R, Sheng Z, Liao E (2008) Comparison of the effects of genistein and zoledronic acid on the bone loss in OPG-deficient mice. Bone 42:950–959

    Article  CAS  PubMed  Google Scholar 

  25. 25.

    Kobayashi Y, Udagawa N, Takahashi N (2009) Action of RANKL and OPG for osteoclastogenesis. Crit Rev Eukaryot Gene Expr 19:61–72

    CAS  PubMed  Google Scholar 

  26. 26.

    Kearns AE, Khosla S, Kostenuik PJ (2008) Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev 29:155–192

    Article  CAS  PubMed  Google Scholar 

  27. 27.

    Yano K, Tsuda E, Washida N, Kobayashi F, Goto M, Harada A, Ikeda K, Higashio K, Yamada Y (1999) Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: increased serum concentrations in postmenopausal women with osteoporosis. J Bone Miner Res 14:518–527

    Article  CAS  PubMed  Google Scholar 

  28. 28.

    Bae YJ, Kim MH (2010) Calcium and magnesium supplementation improves serum OPG/RANKL in calcium-deficient ovariectomized rats. Calcif Tissue Int 87:365–372

    Article  CAS  PubMed  Google Scholar 

  29. 29.

    Kassi E, Pervanidou P, Kaltsas G, Chrousos G (2011) Metabolic syndrome: definitions and controversies. BMC Med 9:48

    Article  PubMed  Google Scholar 

  30. 30.

    Reaven GM (2011) The metabolic syndrome: time to get off the merry-go-round? J Intern Med 269:127–136

    Article  CAS  PubMed  Google Scholar 

  31. 31.

    Ahmed LA, Schirmer H, Berntsen GK, Fonnebo V, Joakimsen RM (2006) Features of the metabolic syndrome and the risk of non-vertebral fractures: the Tromso Study. Osteoporos Int 17:426–432

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    Kinjo M, Setoguchi S, Solomon DH (2007) Bone mineral density in adults with the metabolic syndrome: analysis in a population-based US sample. J Clin Endocrinol Metab 92:4161–4164

    Article  CAS  PubMed  Google Scholar 

  33. 33.

    Von Muhlen D, Safii S, Jassal SK, Svartberg J, Barrett-Connor E (2007) Associations between the metabolic syndrome and bone health in older men and women: the Rancho Bernardo Study. Osteoporos Int 18:1337–1344

    Article  Google Scholar 

  34. 34.

    Hernández JL, Olmos JM, Pariente E, Martínez J, Valero C, García-Velasco P, Nan D, Llorca J, González-Macías J (2010) Metabolic syndrome and bone metabolism: the Camargo Cohort study. Menopause 17:955–961

    Article  PubMed  Google Scholar 

  35. 35.

    Jeon YK, Lee JG, Kim SS, Kim BH, Kim SJ, Kim YK, Kim IJ (2011) Association between bone mineral density and metabolic syndrome in pre- and postmenopausal women. Endocr J 58:87–93

    Article  PubMed  Google Scholar 

  36. 36.

    Hwang DK, Choi HJ (2010) The relationship between low bone mass and metabolic syndrome in Korean women. Osteoporos Int 21:425–431

    Article  PubMed  Google Scholar 

  37. 37.

    Tseng YH, Huang KC, Liu ML, Shu WT, Sheu WH (2009) Association between metabolic syndrome (MS) and bone mineral loss: a cross-sectional study in Puli Township in Taiwan. Arch Gerontol Geriatr 49(Suppl 2):S37–S40

    Article  PubMed  Google Scholar 

  38. 38.

    Zillikens MC, Uitterlinden AG, van Leeuwen JP, Berends AL, Henneman P, van Dijk KW, Oostra BA, van Duijn CM, Pols HA, Rivadeneira F (2010) The role of body mass index, insulin, and adiponectin in the relation between fat distribution and bone mineral density. Calcif Tissue Int 86:116–125

    Article  CAS  PubMed  Google Scholar 

  39. 39.

    Morin S, Tsang JF, Leslie WD (2009) Weight and body mass index predict bone mineral density and fractures in women aged 40 to 59 years. Osteoporos Int 20:363–370

    Article  CAS  PubMed  Google Scholar 

  40. 40.

    Morin S, Leslie WD, Manitoba Bone Density Program (2009) High bone mineral density is associated with high body mass index. Osteoporos Int 20:1267–1271

    Article  CAS  PubMed  Google Scholar 

  41. 41.

    Zhao LJ, Liu YJ, Liu PY, Hamilton J, Recker RR, Deng HW (2007) Relationship of obesity with osteoporosis. J Clin Endocrinol Metab 92:1640–1646

    Article  CAS  PubMed  Google Scholar 

  42. 42.

    Greco EA, Fornari R, Rossi F, Santiemma V, Prossomariti G, Annoscia C, Aversa A, Brama M, Marini M, Donini LM, Spera G, Lenzi A, Lubrano C, Migliaccio S (2010) Is obesity protective for osteoporosis? Evaluation of bone mineral density in individuals with high body mass index. Int J Clin Pract 64:817–820

    Article  CAS  PubMed  Google Scholar 

  43. 43.

    Núñez NP, Carpenter CL, Perkins SN, Berrigan D, Jaque SV, Ingles SA, Bernstein L, Forman MR, Barrett JC, Hursting SD (2007) Extreme obesity reduces bone mineral density: complementary evidence from mice and women. Obesity (Silver Spring) 15:1980–1987

    Article  Google Scholar 

  44. 44.

    Cao JJ, Sun L, Gao H (2010) Diet-induced obesity alters bone remodeling leading to decreased femoral trabecular bone mass in mice. Ann N Y Acad Sci 1192:292–297

    Article  CAS  PubMed  Google Scholar 

  45. 45.

    Russell M, Mendes N, Miller KK, Rosen CJ, Lee H, Klibanski A, Misra M (2010) Visceral fat is a negative predictor of bone density measures in obese adolescent girls. J Clin Endocrinol Metab 95:1247–1255

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants 30872708, 81000122, and 81070246 from the China National Natural Scientific Foundation and the Science and Technology Project of Changsha City (K1009020-31).

Conflicts of interest

None.

Author information

Affiliations

Authors

Corresponding author

Correspondence to E.-Y. Liao.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Xie, H., Xie, PL., Luo, XH. et al. Omentin-1 exerts bone-sparing effect in ovariectomized mice. Osteoporos Int 23, 1425–1436 (2012). https://doi.org/10.1007/s00198-011-1697-8

Download citation

Keywords

  • Bone mineral density
  • Omentin-1
  • Osteoblast
  • Osteoclast