{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T15:07:27Z","timestamp":1788188847744,"version":"build-2803163510"},"reference-count":61,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004508","name":"Prince of Songkla University","doi-asserted-by":"publisher","award":["SCI6202084S"],"award-info":[{"award-number":["SCI6202084S"]}],"id":[{"id":"10.13039\/501100004508","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Office of National Higher Education Science Research and Innovation Policy Council through Program Management Unit for Competitiveness","award":["C10F650224"],"award-info":[{"award-number":["C10F650224"]}]},{"name":"Thailand\u2019s Education Hub for the Southern Region of ASEAN Countries","award":["PHD\/2560"],"award-info":[{"award-number":["PHD\/2560"]}]},{"DOI":"10.13039\/501100022284","name":"Graduate School, Prince of Songkla University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100022284","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Prince of Songkla University Science Park","award":["002.1\/67"],"award-info":[{"award-number":["002.1\/67"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Inositol is a natural carbocyclic sugar that plays an essential role in regulating the vital cellular functions of plants and animals. Existing research has explored methyl derivatives of inositol, reporting on their various biological activities, including antitumor, anti-inflammatory, and anti-osteoporosis activities. Our previous study demonstrated that L-quebrachitol, a methyl derivative of inositol, enhances osteoblastogenesis and bone formation; however, its effect on osteoclastogenesis remains unclear. Consequently, we aimed to investigate the effect of L-quebrachitol on receptor activator of nuclear factor-\u03baB ligand-induced osteoclastogenesis in pre-osteoclastic RAW 264.7 cells, and bone resorption in an ovariectomized rat model. The results revealed that L-quebrachitol suppressed RANK-mediated signaling, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB) and Fos proto-oncogene (cFOS) pathways, at both the gene and protein levels. Moreover, the critical transcription factor for osteoclastogenesis, nuclear factor of activated T cells c1 (NFATc1), was downregulated. Inhibition of osteoclast-associated marker genes encoding proteolytic enzymes, such as tartrate-resistant acid phosphatase (TRAP), matrix metallopeptidase 9 (MMP-9), and cathepsin K, led to reduced formation of TRAP-positive multinucleated cells and resorption pits. In addition, proteasome subunit alpha type-5 (PSMA5), which is involved in the degradation of the NF-\u03baB inhibitor, was also suppressed. In particular, the animal study clearly supported the bone homeostasis property of the agent by increasing the BV\/TV (bone volume\/total volume) and Tb.Th (trabecular thickness) in ovariectomized rats. These findings demonstrate the dose-dependent inhibitory effect of L-quebrachitol on osteoclastogenesis through the modulation of RANK-mediated signaling pathways and prevention of bone loss in an animal model. However, further exploration of the potential of L-quebrachitol as an effective approach for osteoporosis is required.<\/jats:p>","DOI":"10.3390\/biom16010168","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T11:27:58Z","timestamp":1768908478000},"page":"168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["L-Quebrachitol Attenuates RANKL-Induced Osteoclastogenesis and Bone Resorption in Ovariectomized Rat Model"],"prefix":"10.3390","volume":"16","author":[{"given":"Purithat","family":"Rattajak","sequence":"first","affiliation":[{"name":"Division of Health and Applied Science (Biochemistry), Faculty of Science, Prince of Songkla University, Hat-Yai 90110, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2845-8155","authenticated-orcid":false,"given":"Aratee","family":"Aroonkesorn","sequence":"additional","affiliation":[{"name":"Division of Health and Applied Science (Biochemistry), Faculty of Science, Prince of Songkla University, Hat-Yai 90110, Songkhla, Thailand"},{"name":"Center of Excellence for Biochemistry, Faculty of Science, Prince of Songkla University, Hat-Yai 90110, Songkhla, Thailand"},{"name":"Center for Natural Rubber Latex Biotechnology Research and Innovation Development, Prince of Songkla University, Hat-Yai 90110, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanintorn","family":"Yodthong","sequence":"additional","affiliation":[{"name":"Division of Health and Applied Science (Biochemistry), Faculty of Science, Prince of Songkla University, Hat-Yai 90110, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8704-5695","authenticated-orcid":false,"given":"Acharaporn","family":"Issuriya","sequence":"additional","affiliation":[{"name":"Division of Health and Applied Science (Physiology), Faculty of Science, Prince of Songkla University, Hat-Yai 90110, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siriluk","family":"Maskaew","sequence":"additional","affiliation":[{"name":"Center for Natural Rubber Latex Biotechnology Research and Innovation Development, Prince of Songkla University, Hat-Yai 90110, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6526-0565","authenticated-orcid":false,"given":"Carl","family":"Smythe","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rapepun","family":"Wititsuwannakul","sequence":"additional","affiliation":[{"name":"Center for Natural Rubber Latex Biotechnology Research and Innovation Development, Prince of Songkla University, Hat-Yai 90110, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3391-2749","authenticated-orcid":false,"given":"Thanawat","family":"Pitakpornpreecha","sequence":"additional","affiliation":[{"name":"Division of Health and Applied Science (Biochemistry), Faculty of Science, Prince of Songkla University, Hat-Yai 90110, Songkhla, Thailand"},{"name":"Center of Excellence for Biochemistry, Faculty of Science, Prince of Songkla University, Hat-Yai 90110, Songkhla, Thailand"},{"name":"Center for Natural Rubber Latex Biotechnology Research and Innovation Development, Prince of Songkla University, Hat-Yai 90110, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00774-020-01162-6","article-title":"Osteoclast differentiation by RANKL and OPG signaling pathways","volume":"39","author":"Udagawa","year":"2021","journal-title":"J. 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