DOI QR코드

DOI QR Code

Limonium Tetragonum Enhances Osteoblastogenesis while Suppressing the Adipocyte Differentiation

  • Kim, Jung-Ae (Marine Biotechnology Center for Pharmaceuticals and Foods, Silla University) ;
  • Ahn, Byul-Nim (Marine Biotechnology Center for Pharmaceuticals and Foods, Silla University) ;
  • Oh, Jung Hwan (Marine Biotechnology Center for Pharmaceuticals and Foods, Silla University) ;
  • Karadeniz, Fatih (Marine Biotechnology Center for Pharmaceuticals and Foods, Silla University) ;
  • Lee, Jung Im (Marine Biotechnology Center for Pharmaceuticals and Foods, Silla University) ;
  • Seo, Youngwan (Division of Marine Bioscience, Korea Maritime and Ocean University) ;
  • Kong, Chang-Suk (Marine Biotechnology Center for Pharmaceuticals and Foods, Silla University)
  • Received : 2021.12.01
  • Accepted : 2022.01.09
  • Published : 2022.03.30

Abstract

Halophytes are plants that live in harsh environments in coastal regions and are known for their diverse chemical compositions. Limonium tetragonum, a halophyte endemic to Korean shores, is known for its bioactive compounds and is utilized in folk medicine. In this study L. tetragonum extract (LHE) was used to determine and evaluate its anti-osteoporotic properties. Pre-adipocyte and pre-osteoblasts were induced to differentiate along with LHE treatment, and their differentiation was evaluated using differentiation markers. LHE treatment decreased lipid accumulation in 3T3-L1 preadipocytes during adipogenesis. Results indicated that the LHE treatment also decreased the levels of key adipogenic transcription factors: PPARγ, SREBP1c, and C/EBPα. Enhancing osteoblastogenesis by LHE treatment was confirmed in osteoblastogenesis-induced MC3T3-E1 pre-osteoblasts. Cells treated with LHE resulted in increased calcification and alkaline phosphatase (ALP) activity compared with osteoblasts without LHE treatment. Pro-osteogenic and anti-adipogenic effects were also confirmed in D1 murine mesenchymal stromal cells which are capable of differentiation into both adipocytes and osteoblasts. LHE hindered adipogenesis and enhanced osteoblastogenesis in D1 MSCs in a similar fashion. In conclusion, L. tetragonum is believed to possess the potential to be utilized as a nutraceutical ingredient against osteoporotic conditions.

Keywords

Acknowledgement

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2020R1I1A3070750), and was supported by the BB21plus funded by Busan Metropolitan City and Busan Institute for Talent & Lifelong Education (BIT).

References

  1. Al-Anazi AF, Qureshi VF, Javaid K, Qureshi S (2011) Preventive effects of phytoestrogens against postmenopausal osteoporosis as compared to the available therapeutic choices: an overview. J Nat Sci Biol Med 2:154-163 https://doi.org/10.4103/0976-9668.92322
  2. An J, Yang H, Zhang Q, Liu C, Zhao J, Zhang L, Chen B (2016) Natural products for treatment of osteoporosis: the effects and mechanisms on promoting osteoblast-mediated bone formation. Life Sci 147:46-58 https://doi.org/10.1016/j.lfs.2016.01.024
  3. Bae MJ, Karadeniz F, Lee SG, Seo Y, Kong CS (2016) Inhibition of MMP-2 and MMP-9 Activities by Limonium tetragonum Extract. Prev Nutr Food Sci 21:38-43 https://doi.org/10.3746/PNF.2016.21.1.38
  4. Bishop GB, Einhorn TA (2007) Current and future clinical applications of bone morphogenetic proteins in orthopaedic trauma surgery. Int Orthop 31:721-727 https://doi.org/10.1007/s00264-007-0424-8
  5. Bone HG, Mc Clung MR, Roux C, Rec ker RR, Eisman JA, Verbruggen N, Hustad CM, Da Silva C, Santora AC, Ince BA (2009) Odanacatib, a cathepsin-K inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone density. J Bone Miner Res 25:34-41
  6. Colaianni G, Brunetti G, Faienza MF, Colucci S, Grano M (2014) Osteoporosis and obesity: role of Wnt pathway in human and murine models. World J Orthop 5:242-246 https://doi.org/10.5312/wjo.v5.i3.242
  7. Golub EE, Boesze-Battaglia K (2007) The role of alkaline phosphatase in mineralization. Curr Opin Orthop 18:444-448 https://doi.org/10.1097/BCO.0b013e3282630851
  8. Guan M, Yao W, Liu R, Lam KS, Nolta J, Jia J, Panganiban B, Meng L, Zhou P, Shahnazari M, Ritchie RO, Lane NE (2012) Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass. Nat Med 18:456-462 https://doi.org/10.1038/nm.2665
  9. Hu L, Yin C, Zhao F, Ali A, Ma J, Qian A (2018) Mesenchymal stem cells: cell fate decision to osteoblast or adipocyte and application in osteoporosis treatment. Int J Mol Sci 19:360 https://doi.org/10.3390/ijms19020360
  10. Ing SW, Belury MA (2011) Impact of conjugated linoleic acid on bone physiology: proposed mechanism involving inhibition of adipogenesis. Nutr Rev 69:123-131 https://doi.org/10.1111/j.1753-4887.2011.00376.x
  11. James AW (2013) Review of signaling pathways governing MSC osteogenic and adipogenic differentiation. Scientifica 2013:684736 https://doi.org/10.1155/2013/684736
  12. Jia M, Nie Y, Cao DP, Xue YY, Wang JS, Zhao L, Rahman K, Zhang QY, Qin LP (2012) Potential antiosteoporotic agents from plants: a comprehensive review. Evid-Based Compl Alt 2012:364604
  13. Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M (2001) Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology 2:165-171 https://doi.org/10.1023/A:1011513223894
  14. Karadeniz F, Kim JA, Ahn BN, Kwon MS, Kong CS (2014) Effect of Salicornia herbacea on osteoblastogenesis and adipogenesis in vitro. Mar Drugs 12:5132-5147 https://doi.org/10.3390/md12105132
  15. Kawai M, Rosen CJ (2010) PPARγ: a circadian transcription factor in adipogenesis and osteogenesis. Nat Rev Endocrinol 6:629-636 https://doi.org/10.1038/nrendo.2010.155
  16. Komm BS, Chines AA (2012) An update on selective estrogen receptor modulators for the prevention and treatment of osteoporosis. Maturitas 71:221-226 https://doi.org/10.1016/j.maturitas.2011.11.018
  17. Kraenzlin ME, Meier C (2011) Parathyroid hormone analogues in the treatment of osteoporosis. Nat Rev Endocrinol 7:647-656 https://doi.org/10.1038/nrendo.2011.108
  18. Lecka-Czernik B (2010) PPARs in bone: the role in bone cell differentiation and regulation of energy metabolism. Curr Osteoporos Rep 8:84-90 https://doi.org/10.1007/s11914-010-0016-1
  19. Lee JI, Kong CS, Jung ME, Hong JW, Noh I, Seo Y (2011) Peroxynitrite-scavenging activity of the halophyte Limonium tetragonum. Ocean Polar Res 33:185-191 https://doi.org/10.4217/OPR.2011.33.2.185
  20. Matsubara T, Kida K, Yamaguchi A, Hata K, Ichida F, Meguro H, Aburatani H, Nishimura R, Yoneda T (2008) BMP2 regulates Osterix through Msx2 and Runx2 during osteoblast differentiation. J Biol Chem 283:29119-29125 https://doi.org/10.1074/jbc.M801774200
  21. Ominsky MS, Li C, Li X, Tan HL, Lee E, Barrero M, Asuncion FJ, Dwyer D, Han CY, Vlasseros F, Samadfam R, Jolette J, Smith SY, Stolina M, Lacey DL, Simonet WS, Paszty C, Li G, Ke HZ (2011) Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of nonfractured bones. J Bone Miner Res 26:1012-1021 https://doi.org/10.1002/jbmr.307
  22. Otto S, Sotlar K, Ehrenfeld M, Pautke C (2011) Osteonecrosis of the jaw as a possible rare side effect of annual bisphosphonate administration for osteoporosis: a case report. J Med Case Rep 5:477 https://doi.org/10.1186/1752-1947-5-477
  23. Rizzoli R, Cooper C, Reginster JY, Abrahamsen B, Adachi JD, Brandi ML, Bruyere O, Compston J, Ducy P, Ferrari S, Harvey NC, Kanis JA, Karsenty G, Laslop A, Rabenda V, Vestergaard P (2012) Antidepressant medications and osteoporosis. Bone 51:606-613 https://doi.org/10.1016/j.bone.2012.05.018
  24. Veronesi F, Torricelli P, Borsari V, Tschon M, Rimondini L, Fini M (2011) Mesenchymal stem cells in the aging and osteoporotic population. Crit Rev Eukar Gene 21:363-377 https://doi.org/10.1615/CritRevEukarGeneExpr.v21.i4.60
  25. Wan Y, Chong LW, Evans RM (2007) PPAR-γ regulates osteoclastogenesis in mice. Nat Med 13:1496-1503 https://doi.org/10.1038/nm1672
  26. Wang C, Meng H, Wang X, Zhao C, Peng J, Wang Y (2016) Differentiation of bone marrow mesenchymal stem cells in osteoblasts and adipocytes and its role in treatment of osteoporosis. Med Sci Monit 22:226-233 https://doi.org/10.12659/MSM.897044
  27. Watts NB, Diab DL (2010) Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab 95:1555-1565 https://doi.org/10.1210/jc.2009-1947
  28. Woo C, Gao G, Wade S, Hochberg MC (2010) Gastrointestinal side effects in postmenopausal women using osteoporosis therapy: 1-year findings in the POSSIBLE US study. Curr Med Res Opin 26:1003-1009 https://doi.org/10.1185/03007991003633603
  29. Xu C, Wang J, Zhu T, Shen Y, Tang X, Fang L, Xu Y (2016) Cross-talking between PPAR and WNT signaling and its regulation in mesenchymal stem cell differentiation. Curr Stem Cell Res Ther 11:247-254 https://doi.org/10.2174/1574888X10666150723145707
  30. Yang MH, Kim NH, Heo JD, Sung SH, Jeong EJ (2014) Hepatoprotective effects of Limonium tetragonum, edible medicinal halophyte growing near seashores. Pharmacogn Mag 10: S563-S568
  31. Zhou BO, Yue R, Murphy MM, Peyer JG, Morrison SJ (2014) Leptin-receptor- expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell Stem Cell 15:154-168 https://doi.org/10.1016/j.stem.2014.06.008
  32. Zhuang H, Zhang X, Zhu C, Tang X, Yu F, Shang WG, Cai X (2016) Molecular mechanisms of PPAR-γ; governing MSC osteogenic and adipogenic differentiation. Curr Stem Cell Res Ther 11:255-264 https://doi.org/10.2174/1574888X10666150531173309