Water Extract of Tendril of Duch. Suppresses RANKL-induced Osteoclastogenesis by Down-regulating P38 and ERK Signaling

Overview

Journal Int J Med Sci

Specialty General Medicine

Date 2020 Mar 27

PMID 32210713

Citations 4

Authors

Joo-Hee Choi

Ah-Ra Jang

Ha-Na Jeong

Kiok Kim

Young-Min Kim

Jeong-Yong Cho

Jong-Hwan Park

Affiliations

Soon will be listed here.

Abstract

Pumpkin () is a natural product that is commonly used in folk medicine. However, the inhibitory effect and molecular mechanisms of tendril of Duch. (TCMD) on osteoclast differentiation have yet to be clearly elucidated. Thus, the present study aimed to investigate the effect and underlying mechanism of water extract of TCMD on osteoclast differentiation. Bone marrow-derived macrophages (BMDMs), osteoclast precursors, were cultured with macrophage colony stimulating factor (M-CSF) 30 ng/ml and receptor activator of nuclear factor-kappa B ligand (RANKL) 100 ng/ml for four days. We investigated the effect of TCMD on RANKL-induced osteoclast differentiation, tartrate-resistant acid phosphatase (TRAP) staining, F-actin ring formation, and bone resorption assay. RANKL signaling pathways were determined through Western blotting, and osteoclast differentiation marker genes were confirmed by Real-time PCR. TCMD inhibited the RANKL-induced osteoclast differentiation in a dose-dependent manner without cytotoxicity. Further, F-actin ring formation and bone resorption were reduced by TCMD in RANKL-treated BMDMs. In addition, TCMD decreased the phosphorylation of p38 and ERK as well as the expression of osteoclast-related genes in BMDMs treated with RANKL. These findings suggest that TCMD may have preventive and therapeutic effects for destructive bone diseases.

Citing Articles

Extracellular Vesicles from Human Adipose Tissue-Derived Mesenchymal Stem Cells Suppress RANKL-Induced Osteoclast Differentiation via miR122-5p.

Choi J, Sung S, Kang K, Lee S, Sung M, Park W Biochem Genet. 2023; 62(4):2830-2852.

PMID: 38017286 DOI: 10.1007/s10528-023-10569-5.

Cilengitide inhibits osteoclast adhesion through blocking the αβ-mediated FAK/Src signaling pathway.

Guo D, Chen Z, Fu Y, Li Y, Chen M, Wu J Heliyon. 2023; 9(7):e17841.

PMID: 37539209 PMC: 10395300. DOI: 10.1016/j.heliyon.2023.e17841.

Pro-Osteogenic Properties of () Leaf Extracts: Data from In Vitro Human Primary Cell Cultures.

Lambertini E, Penolazzi L, Pellielo G, Pipino C, Pandolfi A, Fiorito S Nutrients. 2021; 13(8).

PMID: 34444791 PMC: 8399764. DOI: 10.3390/nu13082633.

New 8---Hydroxylbenzylflavonol Glycosides from Pumpkin ( Duch.) Tendril and Their Osteoclast Differentiation Inhibitory Activities.

Kim K, Choi J, Oh J, Park J, Kim Y, Moon J Molecules. 2020; 25(9).

PMID: 32365620 PMC: 7248980. DOI: 10.3390/molecules25092077.

References

Boyle W, Simonet W, Lacey D . Osteoclast differentiation and activation. Nature. 2003; 423(6937):337-42. DOI: 10.1038/nature01658. View

Kong Y, Yoshida H, Sarosi I, Tan H, Timms E, Capparelli C . OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999; 397(6717):315-23. DOI: 10.1038/16852. View

Kwak H, Lee B, Oh J, Yeon J, Choi S, Cho H . Inhibition of osteoclast differentiation and bone resorption by rotenone, through down-regulation of RANKL-induced c-Fos and NFATc1 expression. Bone. 2009; 46(3):724-31. DOI: 10.1016/j.bone.2009.10.042. View

Armstrong A, Tometsko M, Glaccum M, Sutherland C, Cosman D, Dougall W . A RANK/TRAF6-dependent signal transduction pathway is essential for osteoclast cytoskeletal organization and resorptive function. J Biol Chem. 2002; 277(46):44347-56. DOI: 10.1074/jbc.M202009200. View

Wada T, Nakashima T, Hiroshi N, Penninger J . RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med. 2005; 12(1):17-25. DOI: 10.1016/j.molmed.2005.11.007. View

Lestari B, Walidah Z, Utomo R, Murwanti R, Meiyanto E . Supplementation with extract of pumpkin seeds exerts estrogenic effects upon the uterine, serum lipids, mammary glands, and bone density in ovariectomized rats. Phytother Res. 2019; 33(4):891-900. DOI: 10.1002/ptr.6280. View

Li X, Udagawa N, Itoh K, Suda K, Murase Y, Nishihara T . p38 MAPK-mediated signals are required for inducing osteoclast differentiation but not for osteoclast function. Endocrinology. 2002; 143(8):3105-13. DOI: 10.1210/endo.143.8.8954. View

Kim H, Nam S, Yang S, Kim H, Jeong H . Cucurbita moschata Duch. and its active component, β-carotene effectively promote the immune responses through the activation of splenocytes and macrophages. Immunopharmacol Immunotoxicol. 2016; 38(5):319-26. DOI: 10.1080/08923973.2016.1202960. View

Takayanagi H . The role of NFAT in osteoclast formation. Ann N Y Acad Sci. 2007; 1116:227-37. DOI: 10.1196/annals.1402.071. View

10.

Asagiri M, Sato K, Usami T, Ochi S, Nishina H, Yoshida H . Autoamplification of NFATc1 expression determines its essential role in bone homeostasis. J Exp Med. 2005; 202(9):1261-9. PMC: 2213228. DOI: 10.1084/jem.20051150. View

11.

Hossain M, Lee S, Park N, Birhanu B, Mechesso A, Park J . Enhancement of Lipid Metabolism and Hepatic Stability in Fat-Induced Obese Mice by Fermented Extract. Evid Based Complement Alternat Med. 2018; 2018:3908453. PMC: 5872621. DOI: 10.1155/2018/3908453. View

12.

Yamasaki T, Ariyoshi W, Okinaga T, Adachi Y, Hosokawa R, Mochizuki S . The dectin 1 agonist curdlan regulates osteoclastogenesis by inhibiting nuclear factor of activated T cells cytoplasmic 1 (NFATc1) through Syk kinase. J Biol Chem. 2014; 289(27):19191-203. PMC: 4081954. DOI: 10.1074/jbc.M114.551416. View

13.

Leibbrandt A, Penninger J . RANK/RANKL: regulators of immune responses and bone physiology. Ann N Y Acad Sci. 2008; 1143:123-50. DOI: 10.1196/annals.1443.016. View

14.

Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S . Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A. 1998; 95(7):3597-602. PMC: 19881. DOI: 10.1073/pnas.95.7.3597. View

15.

Kim J, Kim N . Regulation of NFATc1 in Osteoclast Differentiation. J Bone Metab. 2014; 21(4):233-41. PMC: 4255043. DOI: 10.11005/jbm.2014.21.4.233. View

16.

Shim K, Ma J . Pine needles attenuate receptor activator for nuclear factor-B ligand (RANKL)-induced trabecular bone loss by inhibiting osteoclast differentiation. Integr Med Res. 2018; 7(4):374-380. PMC: 6303373. DOI: 10.1016/j.imr.2018.06.006. View

17.

Zaidi M, Blair H, Moonga B, Abe E, Huang C . Osteoclastogenesis, bone resorption, and osteoclast-based therapeutics. J Bone Miner Res. 2003; 18(4):599-609. DOI: 10.1359/jbmr.2003.18.4.599. View

18.

Teitelbaum S . Bone resorption by osteoclasts. Science. 2000; 289(5484):1504-8. DOI: 10.1126/science.289.5484.1504. View

19.

Soysa N, Alles N . NF-kappaB functions in osteoclasts. Biochem Biophys Res Commun. 2008; 378(1):1-5. DOI: 10.1016/j.bbrc.2008.10.146. View

20.

Matsuo K, Irie N . [Transcription factors in osteoclast differentiation]. Nihon Rinsho. 2005; 63(9):1541-6. View