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Inhibition of Osteoclast Differentiation and Promotion of Osteogenic Formation by Wolfiporia extensa Mycelium

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초록

Osteoporosis, Greek for “porous bone,” is a bone disease characterized by a decrease in bone strength, microarchitectural changes in the bone tissues, and an increased risk of fracture. An imbalance of bone resorption and bone formation may lead to chronic metabolic diseases such as osteoporosis. Wolfiporia extensa, known as “Bokryung” in Korea, is a fungus belonging to the family Polyporaceae and has been used as a therapeutic food against various diseases. Medicinal mushrooms, mycelium and fungi, possess approximately 130 medicinal functions, including antitumor, immunomodulating, antibacterial, hepatoprotective, and antidiabetic effects, and are therefore used to improve human health. In this study, we used osteoclast and osteoblast cell cultures treated with Wolfiporia extensa mycelium water extract (WEMWE) and investigated the effect of the fungus on bone homeostasis. Subsequently, we assessed its capacity to modulate both osteoblast and osteoclast differentiation by performing osteogenic and anti-osteoclastogenic activity assays. We observed that WEMWE increased BMP-2-stimulated osteogenesis by inducing Smad-Runx2 signal pathway axis. In addition, we found that WEMWE decreased RANKL-induced osteoclastogenesis by blocking c-Fos/NFATc1 via the inhibition of ERK and JNK phosphorylation. Our results show that WEMWE can prevent and treat bone metabolic diseases, including osteoporosis, by a biphasic activity that sustains bone homeostasis. Therefore, we suggest that WEMWE can be used as a preventive and therapeutic drug.

Abstract

Osteoporosis, Greek for “porous bone,” is a bone disease characterized by a decrease in bone strength, microarchitectural changes in the bone tissues, and an increased risk of fracture. An imbalance of bone resorption and bone formation may lead to chronic metabolic diseases such as osteoporosis. Wolfiporia extensa, known as “Bokryung” in Korea, is a fungus belonging to the family Polyporaceae and has been used as a therapeutic food against various diseases. Medicinal mushrooms, mycelium and fungi, possess approximately 130 medicinal functions, including antitumor, immunomodulating, antibacterial, hepatoprotective, and antidiabetic effects, and are therefore used to improve human health. In this study, we used osteoclast and osteoblast cell cultures treated with Wolfiporia extensa mycelium water extract (WEMWE) and investigated the effect of the fungus on bone homeostasis. Subsequently, we assessed its capacity to modulate both osteoblast and osteoclast differentiation by performing osteogenic and anti-osteoclastogenic activity assays. We observed that WEMWE increased BMP-2-stimulated osteogenesis by inducing Smad-Runx2 signal pathway axis. In addition, we found that WEMWE decreased RANKL-induced osteoclastogenesis by blocking c-Fos/NFATc1 via the inhibition of ERK and JNK phosphorylation. Our results show that WEMWE can prevent and treat bone metabolic diseases, including osteoporosis, by a biphasic activity that sustains bone homeostasis. Therefore, we suggest that WEMWE can be used as a preventive and therapeutic drug.

참고문헌 (54)

  1. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy, "Osteoporosis prevention, diagnosis, and therapy", JAMA, 285, pp.785~795 (2001)
  2. Karsenty G, "Reaching a genetic and molecular understanding of skeletal development", Dev. Cell, 2, pp.389~406 (2002)
  3. Komori T, "Regulation of osteoblast differentiation by transcription factors", J. Cell. Biochem, 99, pp.1233~1239 (2006)
  4. Ponzetti M, "Osteoblast differentiation and signaling: established concepts and emerging topics", Int. J. Mol. Sci, 22, pp.6651~ (2021)
  5. Almalki SG, "Key transcription factors in the differentiation of mesenchymal stem cells", Differentiation, 92, pp.41~51 (2016)
  6. Herpin A, "Cross-talk between the bone morphogenetic protein pathway and other major signaling pathways results in tightly regulated cell-specific outcomes", FEBS J, 274, pp.2977~2985 (2007)
  7. Samee N, "Dlx5, a positive regulator of osteoblastogenesis, is essential for osteoblast-osteoclast coupling", Am. J. Pathol, 173, pp.773~780 (2008)
  8. Capulli M, "Osteoblast and osteocyte: games without frontiers", Arch. Biochem. Biophys, 561, pp.3~12 (2014)
  9. 김우진, "RUNX2-modifying enzymes: therapeutic targets for bone diseases", Experimental and Molecular Medicine, 52, pp.1~7 (2020), 생화학분자생물학회[DOI]
  10. Chen X, "Osteoblast-osteoclast interactions", Connect. Tissue Res, 59, pp.99~107 (2018)
  11. Udagawa N, "Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells", Proc. Natl. Acad. Sci. USA, 87, pp.7260~7264 (1990)
  12. Takahashi N, "Osteoblastic cells are involved in osteoclast formation", Endocrinology, 123, pp.2600~2602 (1988)
  13. Yoshida H, "The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene", Nature, 345, pp.442~444 (1990)
  14. Yasuda H, "Osteoclast differentiation factor is a ligand for osteoprotegerin", osteoclastogenesis-inhibitory factor and is identical to TRANCE, Proc. Natl. Acad. Sci. USA, pp.1998, 95[DOI]
  15. Lee ZH, "Signal transduction by receptor activator of nuclear factor kappa B in osteoclasts", Biochem. Biophys. Res. Commun, 305, pp.211~214 (2003)
  16. Feng X, "RANKing intracellular signaling in osteoclasts", IUBMB Life, 57, pp.389~395 (2005)
  17. Takayanagi H, "Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems", Nat. Rev. Immunol, 7, pp.292~304 (2007)
  18. Takayanagi H, "Inflammatory bone destruction and osteoimmunology", J. Periodont. Res, 40, pp.287~293 (2005)
  19. Grigoriadis AE, "c-Fos: a key regulator of osteoclastmacrophage lineage determination and bone remodeling", Science, 266, pp.443~448 (1994)
  20. Takayanagi H, "Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts", Dev. Cell, 3, pp.889~901 (2002)
  21. Rodan GA, "Therapeutic approaches to bone diseases", Science, 289, pp.1508~1514 (2000)
  22. Teitelbaum SL, "Bone resorption by osteoclasts", Science, 289, pp.1504~1508 (2000)
  23. Skjødt MK, "Side effects of drugs for osteoporosis and metastatic bone disease", Br. J. Clin. Pharmacol, 85, pp.1063~1071 (2019)
  24. Stafford RS, "National trends in osteoporosis visits and osteoporosis treatment, 1988-2003", Arch. Intern. Med, 164, pp.1525~1530 (2004)
  25. Watson J, "Prescribing of hormone therapy for menopause, tibolone, and bisphosphonates in women in the UK between 1991 and 2005", Eur. J. Clin. Pharmacol, 63, pp.843~849 (2007)
  26. Filleul O, "Bisphosphonate-induced osteonecrosis of the jaw: a review of 2,400 patient cases", J. Cancer Res. Clin. Oncol, 136, pp.1117~1124 (2010)
  27. Yuan H, "The traditional medicine and modern medicine from natural products", Molecules, 21, pp.559~ (2016)
  28. Posadzki P, "Adverse effects of herbal medicines: an overview of systematic reviews", Clin. Med. (Lond.), 13, pp.7~12 (2013)
  29. Fijałkowska A, "Medicinal potential of mycelium and fruiting bodies of an arboreal mushroom Fomitopsis officinalis in therapy of lifestyle diseases", Sci. Rep, 10, pp.20081~ (2020)
  30. Berger RG, "Mycelium vs. fruiting bodies of edible fungi-a comparison of metabolites", Microorganisms, 10, pp.1379~ (2022)
  31. Wasser SP, "Medicinal mushroom science: current perspectives, advances, evidences, and challenges", Biomed J, 37, pp.345~356 (2014)
  32. 최수희, "국내 지역별 매립 복령의 성분 및 항산화 활성 비교", 한국균학회지, 44(1), pp.23~30 (2016), 한국균학회
  33. Cuélla MJ, "Two fungal lanostane derivatives as phospholipase A2 inhibitors", J. Nat. Prod, 59, pp.977~979 (1996)
  34. Wu Y, "De novo assembly and transcriptome analysis of sclerotial development in Wolfiporia cocos", Gene, 588, pp.149~155 (2016)
  35. Esteban CI, "Medicinal interest of Poria cocos (= Wolfiporia extensa)", Rev. Iberoam. Micol, 26, pp.103~107 (2009)
  36. Cheng S, "Triterpenes from Poria cocos suppress growth and invasiveness of pancreatic cancer cells through the downregulation of MMP-7", Int. J. Oncol, 42, pp.1869~1874 (2013)
  37. Jiang Y, "Evaluation of anticancer activities of Poria cocos ethanol extract in breast cancer: in vivo and in vitro, identification and mechanism", J. Ethnopharmacol, 257, pp.112851~ (2020)
  38. Hamuro J, "Carboxymethylpachymaran, a new water soluble polysaccharide with marked antitumour activity", Nature, 233, pp.486~488 (1971)
  39. Nukaya H, "Isolation of inhibitors of TPA-induced mouse ear edema from Hoelen, Poria cocos", Chem. Pharm. Bull. (Tokyo), 44, pp.847~849 (1996)
  40. Hwang YH, "Poria cocos ameliorates bone loss in ovariectomized mice and inhibits osteoclastogenesis in vitro", Nutrients, 12, pp.1383~ (2020)
  41. Kim SH, "The dual role of oat bran water extract in bone homeostasis through the regulation of osteoclastogenesis and osteoblast differentiation", Molecules, 23, pp.3119~ (2018)
  42. Rozen S, "Primer3 on the WWW for general users and for biologist programmers", Methods Mol. Biol, 132, pp.365~386 (2000)
  43. Livak KJ, "Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta C(T))method", Methods, 25, pp.402~408 (2001)
  44. Caetano-Lopes J, "Osteoblasts and bone formation", Acta Reumatol. Port, 32, pp.103~110 (2007)
  45. Katagiri T, "Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage", J. Cell Biol, 127, pp.1755~1766 (1994)
  46. Javed A, "Structural coupling of Smad and Runx2 for execution of the BMP2osteogenic signal", J. Biol. Chem, 283, pp.8412~8422 (2008)
  47. Zainal Ariffin SH, "Gene expression profiles for in vitro human stem cell differentiation into osteoblasts and osteoclasts: a systematic review", PeerJ, 10, pp.e14174~ (2022)
  48. Asagiri M, "The molecular understanding of osteoclast differentiation", Bone, 40, pp.251~264 (2007)
  49. Ishida N, "Large scale gene expression analysis of osteoclastogenesis in vitro and elucidation of NFAT2 as a key regulator", J. Biol. Chem, 277, pp.41147~41156 (2002)
  50. Boyle WJ, "Osteoclast differentiation and activation", Nature, 423, pp.337~342 (2003)
  51. Kim SH, "Biofunctional soyasaponin Bb in peanut (Arachis hypogaea L.) sprouts enhances bone morphogenetic protein-2-dependent osteogenic differentiation via activation of runt-related transcription factor 2in C2C12 cells", Phytother. Res, 33, pp.1490~1500 (2019)
  52. Gersbach CA, "Runx2", Cbfa1 stimulates transdifferentiation of primary skeletal myoblasts into a mineralizing osteoblastic phenotype, 2004, pp.300, 406~417
  53. Chen D, "Bone morphogenetic proteins", Growth Fact, 22, pp.233~241 (2004)
  54. Feng XH, "Specificity and versatility in TGF-beta signaling through Smads", Annu. Rev. Cell Dev. Biol, 21, pp.659~693 (2005)

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