Anti‑osteoclastogenic effects of <em>Coriandrum sativum</em> L. via the NF‑κB and ERK‑mediated NFATc1 signaling pathways

Sim,Jung-Sun; Lee,Hwa-Yeong; Yim,Mijung

doi:10.3892/mmr.2022.12849

Anti‑osteoclastogenic effects of Coriandrum sativum L. via the NF‑κB and ERK‑mediated NFATc1 signaling pathways

Authors:
- Jung-Sun Sim
- Hwa-Yeong Lee
- Mijung Yim
View Affiliations

Affiliations: College of Pharmacy, Sookmyung Women's University, Seoul 04310, Republic of Korea
Published online on: September 8, 2022 https://doi.org/10.3892/mmr.2022.12849
Article Number: 333

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Coriandrum sativum L. (CSL) is an aromatic plant that belongs to the Apiaceae family. The present study aimed to determine the effects of the ethanol extract of the aerial part of CSL on osteoclast formation in vitro and in vivo, and the underlying molecular mechanism of its anti‑osteoclastogenic effect. The levels of osteoclast formation and bone resorption were evaluated by tartrate‑resistant acid phosphatase staining and bone resorption pit assays. The expression levels of osteoclast‑related molecules were analyzed by reverse transcription‑quantitative PCR and western blotting. The ethanol extract of CSL suppressed osteoclast formation in a mouse co‑culture system. In osteoblasts, CSL exerted a minor effect on the mRNA ratio of receptor activator of nuclear factor‑κB (NF‑κB) ligand (RANKL) to osteoprotegerin, suggesting a direct effect of CSL on osteoclast precursors. Notably, CSL inhibited RANKL‑induced osteoclast differentiation and bone resorption activity in bone marrow‑derived macrophage cultures. Mechanistically, CSL abolished RANKL‑induced NF‑κB and extracellular signal‑regulated kinase (ERK) MAPK activation, which effectively impaired the induction of c‑Fos and nuclear factor of activated T cells (NFATc1). Finally, the ethanol extract of CSL prevented osteoclast formation in a lipopolysaccharide‑induced calvarial bone loss model in vivo. The findings of the present study suggested that CSL may suppress osteoclast differentiation and function by downregulating the NF‑κB and ERK/c‑Fos/NFATc1 signaling pathways. Thus, CSL could be explored as a potential candidate for the prevention and treatment of osteolytic diseases.

View Figures

View References

1	Teitelbaum SL: Bone resorption by osteoclasts. Science. 289:1504–1508. 2000. View Article : Google Scholar : PubMed/NCBI
2	Tanaka Y, Nakayamada S and Okada Y: Osteoblasts and osteoclasts in bone remodeling and inflammation. Curr Drug Targets Inflamm Allergy. 4:325–328. 2005. View Article : Google Scholar : PubMed/NCBI
3	Zhao X, Patil S, Xu F, Lin X and Qian A: Role of biomolecules in osteoclasts and their therapeutic potential for osteoporosis. Biomolecules. 11:7472021. View Article : Google Scholar : PubMed/NCBI
4	Boyle WJ, Simonet WS and Lacey DL: Osteoclast differentiation and activation. Nature. 423:337–342. 2003. View Article : Google Scholar : PubMed/NCBI
5	Arai F, Miyamoto T, Ohneda O, Inada T, Sudo T, Brasel K, Miyata T, Anderson DM and Suda T: Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors. J Exp Med. 190:1741–1754. 1999. View Article : Google Scholar : PubMed/NCBI
6	Asagiri M and Takayanagi H: The molecular understanding of osteoclast differentiation. Bone. 40:251–264. 2007. View Article : Google Scholar : PubMed/NCBI
7	Feng X: RANKing intracellular signaling in osteoclasts. IUBMB Life. 57:389–395. 2005. View Article : Google Scholar : PubMed/NCBI
8	Grigoriadis AE, Wang ZQ, Cecchini MG, Hofstetter W, Felix R, Fleisch HA and Wagner EF: c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science. 266:443–448. 1994. View Article : Google Scholar : PubMed/NCBI
9	Kim K, Kim JH, Lee J, Jin HM, Lee SH, Fisher DE, Kook H, Kim KK, Choi Y and Kim N: Nuclear factor of activated T cells c1 induces osteoclast-associated receptor gene expression during tumor necrosis factor-related activation-induced cytokine-mediated osteoclastogenesis. J Biol Chem. 208:35209–35216. 2005. View Article : Google Scholar : PubMed/NCBI
10	Kim JH and Kim N: Regulation of NFATc1 in osteoclast differentiation. J Bone Metab. 21:233–241. 2014. View Article : Google Scholar : PubMed/NCBI
11	Rho J, Takami M and Choi Y: Osteoimmunology: Interactions of the immune and skeletal systems. Mol Cells. 17:1–9. 2004.PubMed/NCBI
12	Walsh MC, Kim N, Kadono Y, Rho J, Lee SY, Lorenzo J and Choi Y: Osteoimmunology: Interplay between the immune system and bone metabolism. Annu Rev Immunol. 24:33–63. 2006. View Article : Google Scholar : PubMed/NCBI
13	Laribi B, Kouki K, M'Hamdi M and Bettaieb T: Coriander (Coriandrum sativum L.) and its bioactive constituents. Fitoterapia. 103:9–26. 2015. View Article : Google Scholar : PubMed/NCBI
14	Sahib NG, Anwar F, Gilani AH, Hamid AA, Saari N and Alkharfy KM: Coriander (Coriandrum sativum L.): A potential source of high-value components for functional foods and nutraceuticals-a review. Phytother Res. 27:1439–1456. 2013. View Article : Google Scholar : PubMed/NCBI
15	Takami M, Cho ES, Lee SY, Kamijo R and Yim M: Phosphodiesterase inhibitors stimulate osteoclast formation via TRANCE/RANKL expression in osteoblasts: possible involvement of ERK and p38 MAPK pathways. FEBS Lett. 31:832–838. 2005. View Article : Google Scholar : PubMed/NCBI
16	O'Brien CA, Gubrij I, Lin SC, Saylors RL and Manolagas SC: STAT3 activation in stromal/osteoblastic cells is required for induction of the receptor activator of NF-kappaB ligand and stimulation of osteoclastogenesis by gp130-utilizing cytokines or interleukin-1 but not 1,25-dihydroxyvitamin D3 or parathyroid hormone. J Biol Chem. 274:19301–19308. 1999. View Article : Google Scholar : PubMed/NCBI
17	Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, et al: Osteoprotegerin: A novel secreted protein involved in the regulation of bone density. Cell. 89:309–319. 1997. View Article : Google Scholar : PubMed/NCBI
18	Darnay BG, Ni J, Moore PA and Aggarwal BB: Activation of NF-kappaB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-kappaB-inducing kinase. Identification of a novel TRAF6 interaction motif. J Biol Chem. 274:7724–7731. 1999. View Article : Google Scholar : PubMed/NCBI
19	Ha H, Lee JH, Kim HN, Kim HM, Kwak HB, Lee S, Kim HH and Lee ZH: alpha-Lipoic acid inhibits inflammatory bone resorption by suppressing prostaglandin E2 synthesis. J Immunol. 176:111–117. 2006. View Article : Google Scholar : PubMed/NCBI
20	Wang J, Zheng H and Ma R: Natural occurring compounds inhibit osteoclastogenesis via targeting NFATc1-related signaling pathways. Curr Drug Targets. 21:358–364. 2020. View Article : Google Scholar : PubMed/NCBI
21	Liu C, He Y, Xu X, He L, He B and Kong L: The study of natural compounds targeting RANKL signaling pathway for the treatment of bone diseases. Curr Drug Targets. 21:344–357. 2020. View Article : Google Scholar : PubMed/NCBI
22	Nicolin V, De Tommasi N, Nori SL, Costantinides F, Berton F and Di Lenarda R: Modulatory effects of plant polyphenols on bone remodeling: A prospective view from the bench to bedside. Front Endocrinol (Lausanne). 10:4942019. View Article : Google Scholar : PubMed/NCBI
23	Harsha SN and Anilakumar KR: In vitro free radical scavenging and DNA damage protective property of Coriandrum sativum L. leaves extract. J Food Sci Technol. 51:1533–1539. 2014. View Article : Google Scholar : PubMed/NCBI
24	Mariezcurrena-Berasain MA, Velázquez-Garduño G, Marín-Mendoza PM, Pliego AB, Vega Castillo LF, Carranza BV, Khusro A, Ugbogu EA and Salem AZM: Sensitivity of Coriandrum sativum extract on bacterial pathogens isolated from digestive system of rabbits, and its role on in vitro cecal gas production and fermentation. Microb Pathog. 123:18–23. 2018. View Article : Google Scholar : PubMed/NCBI
25	Wu TT, Tsai CW, Yao HT, Lii CK, Chen HW, Wu YL, Chen PY and Liu KL: Suppressive effects of extracts from the aerial part of Coriandrum sativum L. on LPS-induced inflammatory responses in murine RAW 264.7 macrophages. J Sci Food Agric. 90:1846–1854. 2010. View Article : Google Scholar : PubMed/NCBI
26	Yim MJ: The role of toll-like receptors in osteoclastogenesis. J Bone Metab. 27:227–35. 2020. View Article : Google Scholar : PubMed/NCBI
27	Oganesyan ET, Nersesyan ZM and Parkhomenko AY: Chemical composition of the above-ground part of Coriandrum sativum. Pharm Chem J. 41:149–153. 2007. View Article : Google Scholar
28	Kim TH, Jung JW, Ha BG, Hong JM, Park EK, Kim HJ and Kim SY: The effects of luteolin on osteoclast differentiation, function in vitro and ovariectomy-induced bone loss. J Nutr Biochem. 22:8–15. 2011. View Article : Google Scholar : PubMed/NCBI
29	Doss HM, Samarpita S, Ganesan R and Rasool M: Ferulic acid, a dietary polyphenol suppresses osteoclast differentiation and bone erosion via the inhibition of RANKL dependent NF-kappaB signalling pathway. Life Sci. 207:284–295. 2018. View Article : Google Scholar : PubMed/NCBI
30	Omori A, Yoshimura Y, Deyama Y and Suzuki K: Rosmarinic acid and arbutin suppress osteoclast differentiation by inhibiting superoxide and NFATc1 downregulation in RAW 264.7 cells. Biomed Rep. 3:483–490. 2015. View Article : Google Scholar : PubMed/NCBI
31	Kyung TW, Lee JE, Shin HH and Choi HS: Rutin inhibits osteoclast formation by decreasing reactive oxygen species and TNF-alpha by inhibiting activation of NF-kappaB. Exp Mol Med. 40:52–68. 2008. View Article : Google Scholar : PubMed/NCBI