{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:19:08Z","timestamp":1788153548618,"version":"build-2803163510"},"reference-count":65,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Thailand Science Research and Innovation Fundamental Fund, fiscal year 2025"},{"id":[{"id":"https:\/\/ror.org\/000025p04","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Research Fund of the Chulabhorn International College of Medicine, Thammasat University","award":["T1\/2565"],"award-info":[{"award-number":["T1\/2565"]}]},{"award":["T1\/2565"],"award-info":[{"award-number":["T1\/2565"]}],"id":[{"id":"https:\/\/ror.org\/002yp7f20","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Thammasat Postdoctoral Fellowship","award":["TUPD6\/2569"],"award-info":[{"award-number":["TUPD6\/2569"]}]},{"name":"Thammasat University Research Unit in Innovative Marine Biotechnology and Natural Bio-resources for Sustainable Health and Wellness"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mar. Drugs","Marine Drugs"],"abstract":"<jats:p>Crustacean shell waste from the seafood industry represents an underutilized food waste with the potential to produce chitosan and chitosan oligosaccharides (COS), with promising applications in bone regeneration. However, the molecular mechanisms of COS during osteogenic differentiation remain uncharacterized. In this study, chitosan was extracted from mud crab (Scylla olivacea) shell waste and COS was prepared from chitosan by acid hydrolysis and then characterized by FT-IR and FESEM, confirming the chitosan backbone and a degree of deacetylation (DD) exceeding 80%. The COS treatment in the concentration range of 5\u2013320 \u00b5g\/mL significantly enhanced MC3T3-E1 pre-osteoblast proliferation without cytotoxicity, and it increased alkaline phosphatase (ALP) activity, extracellular matrix mineralization, and Runx2\/osterix (OSX) expression. Transcriptomics of pre-osteoblasts treated with COS at 320 \u00b5g\/mL for 21 days identified 19,643 differentially expressed genes, revealing coordinated activation of multiple osteogenesis-related signaling pathways, including ECM\u2013integrin\/focal adhesion, PI3K-Akt\/MAPK, TGF-\u03b2\/BMP, Wnt\/\u03b2-catenin, and parathyroid hormone (PTH) synthesis. These findings demonstrate that marine-derived COS promotes osteoblast differentiation through the coordinated activation of multiple signaling pathways, providing the first comprehensive transcriptomic characterization of MC3T3-E1 pre-osteoblast directly treated with COS during osteogenic differentiation. Therefore, this study supports the use of COS as a promising bioactive oligosaccharide for bone regeneration and osteoporosis management, and further in vivo and clinical studies are recommended.<\/jats:p>","DOI":"10.3390\/md24090302","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:24:03Z","timestamp":1788150243000},"page":"302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioactive Chitosan Oligosaccharides Derived from Crab Shell Waste Stimulate Osteogenic Differentiation in Pre-Osteoblast Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6307-8986","authenticated-orcid":false,"given":"Supawadee","family":"Duangprom","sequence":"first","affiliation":[{"name":"Chulabhorn International College of Medicine, Thammasat University, Rangsit Campus, Pathumthani 12120, Thailand"},{"name":"Research Unit in Innovative Marine 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