Pleurotus sajor-caju (Fr.) Singer β-1,3-Glucanoligosaccharide (Ps-GOS) Suppresses RANKL-Induced Osteoclast Differentiation and Function in Pre-Osteoclastic RAW 264.7 Cells by Inhibiting the RANK/NFκB/cFOS/NFATc1 Signalling Pathway.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, c1995-

Cell Differentiation*/drug effects ; Oligosaccharides*/pharmacology ; Oligosaccharides*/chemistry ; Osteoclasts*/drug effects ; Osteoclasts*/metabolism ; Osteoclasts*/cytology ; Pleurotus*/chemistry ; Signal Transduction*/drug effects; Animals ; Mice ; beta-Glucans/pharmacology ; beta-Glucans/chemistry ; NF-kappa B/metabolism ; NFATC Transcription Factors/metabolism ; Osteogenesis/drug effects ; Proto-Oncogene Proteins c-fos/metabolism ; RANK Ligand/metabolism ; RAW 264.7 Cells ; Receptor Activator of Nuclear Factor-kappa B/metabolism

Edible grey oyster mushroom, Pleurotus sajor-caju , β (1,3), (1,6) glucan possesses a wide range of biological activities, including anti-inflammation, anti-microorganism and antioxidant. However, its biological activity is limited by low water solubility resulting from its high molecular weight. Our previous study demonstrated that enzymatic hydrolysis of grey oyster mushroom β-glucan using Hevea β-1,3-glucanase isozymes obtains a lower molecular weight and higher water solubility, Pleurotus sajor-caju glucanoligosaccharide (Ps-GOS). Additionally, Ps-GOS potentially reduces osteoporosis by enhancing osteoblast-bone formation, whereas its effect on osteoclast-bone resorption remains unknown. Therefore, our study investigated the modulatory activities and underlying mechanism of Ps-GOS on Receptor activator of nuclear factor kappa-Β ligand (RANKL) -induced osteoclastogenesis in pre-osteoclastic RAW 264.7 cells. Cell cytotoxicity of Ps-GOS on RAW 264.7 cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and its effect on osteoclast differentiation was determined by tartrate-resistant acid phosphatase (TRAP) staining. Additionally, its effect on osteoclast bone-resorptive ability was detected by pit formation assay. The osteoclastogenic-related factors were assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), Western blot and immunofluorescence. The results revealed that Ps-GOS was non-toxic and significantly suppressed the formation of mature osteoclast multinucleated cells and their resorption activity by reducing the number of TRAP-positive cells and pit formation areas in a dose-dependent manner. Additionally, Ps-GOS attenuated the nuclear factor kappa light chain-enhancer of activated B cells' P65 (NFκB-P65) expression and their subsequent master osteoclast modulators, including nuclear factor of activated T cell c1 (NFATc1) and Fos proto-oncogene (cFOS) via the NF-κB pathway. Furthermore, Ps-GOS markedly inhibited RANK expression, which serves as an initial transmitter of many osteoclastogenesis-related cascades and inhibited proteolytic enzymes, including TRAP, matrix metallopeptidase 9 (MMP-9) and cathepsin K (CTK). These findings indicate that Ps-GOS could potentially be beneficial as an effective natural agent for bone metabolic disease.

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Grant No. PHD/2560 to Purithat Rattajak Thailand's Education Hub for the Southern Region of ASEAN Countries; Grant No. PSUIT-PS 011/64 and PSUIT-CoRe 16/64 Master Labs Incorporation Co., Ltd.

Keywords: Pleurotus sajor-caju; glucanoligosaccharide; osteoclastogenesis; osteoporosis

0 (beta-Glucans)
0 (NF-kappa B)
0 (NFATC Transcription Factors)
0 (Nfatc1 protein, mouse)
0 (Oligosaccharides)
0 (Proto-Oncogene Proteins c-fos)
0 (RANK Ligand)
0 (Receptor Activator of Nuclear Factor-kappa B)
0 (Tnfrsf11a protein, mouse)
0 (Tnfsf11 protein, mouse)

Date Created: 20240511 Date Completed: 20240511 Latest Revision: 20240620

20240620

PMC11085266

10.3390/molecules29092113

38731604