{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T01:22:16Z","timestamp":1770513736917,"version":"3.49.0"},"reference-count":44,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,9,9]],"date-time":"2018-09-09T00:00:00Z","timestamp":1536451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Postmenopausal osteoporosis has seriously affected the life quality of elderly women. A natural polymer, chitin, obtained from shells of crab and shrimp, has been widely used in the biomedical field owing to its nontoxicity, biocompatibility, and biodegradability. In this study, natural N-acetyl-d-glucosamine (NAG) was prepared from liquefied chitin. The protective activities of NAG in postmenopausal osteoporosis were evaluated on Sprague Dawley rats and osteoblast-based models. Results showed that oral administration of NAG boosted trabecular bone volume and trabecular numbers. Additionally, the calcium content in the femur and tibia increased, and femoral biomechanical properties improved. Furthermore, NAG supplementation significantly lowered alkaline phosphatase levels and increased calcium content in the serum of ovariectomized rats. In vitro studies showed that NAG markedly promoted cell proliferation and stimulated osteoblast differentiation of mouse calvaria origin MC3T3-E1 cells with increased alkaline phosphatase activity in a concentration-dependent manner. Moreover, NAG effectively protected osteoblasts from oxidative damage induced by hydrogen peroxide. In conclusion, our data provide an additional foundation for dietary supplementation of NAG, which could protect and reverse osteopenia in postmenopausal women.<\/jats:p>","DOI":"10.3390\/molecules23092302","type":"journal-article","created":{"date-parts":[[2018,9,10]],"date-time":"2018-09-10T10:28:57Z","timestamp":1536575337000},"page":"2302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Dietary Natural N-Acetyl-d-Glucosamine Prevents Bone Loss in Ovariectomized Rat Model of Postmenopausal Osteoporosis"],"prefix":"10.3390","volume":"23","author":[{"given":"Zhiwen","family":"Jiang","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266235, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Li","sequence":"additional","affiliation":[{"name":"Qingdao Biotemed Biomaterial Co., Ltd., Qingdao 266101, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266235, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baoqin","family":"Han","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266235, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanshun","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanfei","family":"Peng","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266235, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/S0140-6736(10)62349-5","article-title":"Osteoporosis: Now and the future","volume":"377","author":"Rachner","year":"2011","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.biopha.2016.09.045","article-title":"Animal models for glucocorticoid-induced postmenopausal osteoporosis: An updated review","volume":"84","author":"Zhang","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"E430","DOI":"10.1152\/ajpendo.00140.2004","article-title":"Effects of endogenous estrogen on renal calcium and phosphate handling in elderly women","volume":"288","author":"Dick","year":"2005","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e971","DOI":"10.7717\/peerj.971","article-title":"Identification of mir-194-5p as a potential biomarker for postmenopausal osteoporosis","volume":"3","author":"Meng","year":"2015","journal-title":"Peerj"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.maturitas.2013.05.021","article-title":"2013 up-date of the consensus statement of the spanish menopause society on postmenopausal osteoporosis","volume":"76","author":"Mendoza","year":"2013","journal-title":"Maturitas"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s00774-004-0596-x","article-title":"Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the japanese society for bone and mineral research (2004)","volume":"23","author":"Nawata","year":"2005","journal-title":"J. Bone Miner. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s00198-005-1957-6","article-title":"A new concept for bisphosphonate therapy: A rationale for the development of monthly oral dosing of ibandronate","volume":"17","author":"Reginster","year":"2006","journal-title":"Osteoporos. Int."},{"key":"ref_8","first-page":"184","article-title":"Bone quality: Understanding what matters","volume":"4","author":"Burr","year":"2004","journal-title":"J. Musculoskel. Neuron"},{"key":"ref_9","first-page":"485","article-title":"Sequential non-traumatic femoral shaft fractures in a patient on long-term alendronate","volume":"13","author":"Cheung","year":"2007","journal-title":"Hong Kong Med. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1056\/NEJMc0707493","article-title":"Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate","volume":"358","author":"Lenart","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Rahnama, M., Jastrz\u0119bskajamrogiewicz, I., Jamrogiewicz, R., and Trybek, G. (2015). Analysis of the influence of hormone replacement therapy on osteocalcin gene expression in postmenopausal women. BioMed Res. Int., 416929.","DOI":"10.1155\/2015\/416929"},{"key":"ref_12","first-page":"321","article-title":"Chitin and chitosan: Novel biomaterials waiting for future developments","volume":"21","author":"Dutta","year":"2004","journal-title":"J. Polym. Mater."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s13726-014-0225-z","article-title":"Preparation and application of chitin and its derivatives: A review","volume":"23","author":"Barikani","year":"2014","journal-title":"Iran. Polym. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0144-8617(03)00170-X","article-title":"Enhanced healing of cartilaginous injuries by N-acetyl-d-glucosamine and glucuronic acid","volume":"54","author":"Tamai","year":"2003","journal-title":"Carbohydr. Polym."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.3390\/molecules18011015","article-title":"Chitosan rate of uptake in hek293 cells is influenced by soluble versus microparticle state and enhanced by serum-induced cell metabolism and lactate-based media acidification","volume":"18","author":"Hoemann","year":"2013","journal-title":"Molecules"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/S1063-4584(03)00026-8","article-title":"Glucosamine and chondroitin sulfate: Biological response modifiers of chondrocytes under simulated conditions of joint stress","volume":"11","author":"Lippiello","year":"2003","journal-title":"Osteoarthr. Cartilage"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/cei.12313","article-title":"Collagen-induced arthritis: Severity and immune response attenuation using multivalent n-acetyl glucosamine","volume":"177","author":"Richter","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S0144-8617(02)00192-3","article-title":"Enzymatic production of N-acetyl-d-glucosamine from chitin. Degradation study of n-acetylchitooligosaccharide and the effect of mixing of crude enzymes","volume":"51","author":"Sashiwa","year":"2003","journal-title":"Carbohydr. Polym."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.joca.2007.02.010","article-title":"Modulation of articular chondrocyte proliferation and anionic glycoconjugate synthesis by glucosamine (glcn), n-acetyl glcn (glcnac) glcn sulfate salt (glcn. s) and covalent glucosamine sulfates (glcn-so4)","volume":"15","author":"Terry","year":"2007","journal-title":"Osteoarthr. Cartilage"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.3390\/ijms12021187","article-title":"N-acetyl glucosamine obtained from chitin by chitin degrading factors in chitinbacter tainanesis","volume":"12","author":"Chen","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.3390\/md8092493","article-title":"N-acetylglucosamine: Production and applications","volume":"8","author":"Chen","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.ijbiomac.2018.02.056","article-title":"Production of chitinase from escherichia fergusonii, chitosanase from chryseobacterium indologenes, comamonas koreensis and its application in n-acetylglucosamine production","volume":"112","author":"Kim","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0891-5849(01)00610-4","article-title":"Oxidative stress modulates osteoblastic differentiation of vascular and bone cells","volume":"31","author":"Mody","year":"2001","journal-title":"Free Radical Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/0891-5849(94)00198-S","article-title":"Superoxide and hydrogen peroxide in relation to mammalian cell proliferation","volume":"18","author":"Burdon","year":"1995","journal-title":"Free Radical Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1530\/eje.0.1500841","article-title":"Selenium has a protective role in caspase-3-dependent apoptosis induced by H2O2 in primary cultured pig thyrocytes","volume":"150","author":"Demelash","year":"2004","journal-title":"Eur. J. Endocrinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1123\/ijsnem.22.1.1","article-title":"Swimming\u2019s prevention of ovariectomy-induced obesity through activation of skeletal-muscle ppar\u03b1","volume":"22","author":"Jeong","year":"2012","journal-title":"Int. J. Sport Nutr. Exerc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"488","DOI":"10.22203\/eCM.v021a37","article-title":"Prediction of in vivo bone forming potency of bone marrow-derived human mesenchymal stem cells","volume":"21","author":"Janicki","year":"2011","journal-title":"Eur. Cells Mater."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1007\/s10439-014-1027-3","article-title":"Improving the estimate of the effective elastic modulus derived from three-point bending tests of long bones","volume":"42","author":"Kourtis","year":"2014","journal-title":"Ann. Biomed. Eng."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3805","DOI":"10.1155\/2013\/506593","article-title":"The use of injectable chitosan\/nanohydroxyapatite\/collagen composites with bone marrow mesenchymal stem cells to promote ectopic bone formation in vivo","volume":"2013","author":"Yu","year":"2013","journal-title":"J. Nanomater."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s00774-015-0665-3","article-title":"The importance of assessing the rate of bone turnover and the balance between bone formation and bone resorption during daily teriparatide administration for osteoporosis: A pilot study","volume":"34","author":"Nakatoh","year":"2016","journal-title":"J. Bone Miner. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.msec.2005.01.014","article-title":"Towards bone replacement materials from calcium phosphates via rapid prototyping and ceramic gelcasting","volume":"25","author":"Woesz","year":"2005","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1159\/000151747","article-title":"Transcriptional regulation of osteoblasts","volume":"189","author":"Franceschi","year":"2009","journal-title":"Cells Tissues Org."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3111","DOI":"10.1096\/fasebj.4.13.2210157","article-title":"Relationship of cell growth to the regulation of tissue-specific gene expression during osteoblast differentiation","volume":"4","author":"Stein","year":"1990","journal-title":"FASEB J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/j.1749-6632.1960.tb49972.x","article-title":"Histochemical observation on enzymatic processes in bone and teeth","volume":"85","author":"Burstone","year":"1960","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"ref_35","first-page":"6001","article-title":"Bisphosphonates directly regulate cell proliferation, differentiation, and gene expression in human osteoblasts","volume":"60","author":"Reinholz","year":"2000","journal-title":"Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1749-6632.1999.tb07814.x","article-title":"Fundamental aspects of reactive oxygen species, or what\u2019s the matter with oxygen","volume":"893","author":"Fridovich","year":"1999","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Voronova, V., Zhudenkov, K., Helmlinger, G., and Peskov, K. (2017). Interpretation of metabolic memory phenomenon using a physiological systems model: What drives oxidative stress following glucose normalization. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171781"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.ajpath.2013.11.011","article-title":"Bone matrix, cellularity, and structural changes in a rat model with high-turnover osteoporosis induced by combined ovariectomy and a multiple-deficient diet","volume":"184","author":"Govindarajan","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1007\/s007020050102","article-title":"Clinical neurochemistry: Developments in dementia research based on brain bank material","volume":"105","author":"Perry","year":"1998","journal-title":"J. Neural Transm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.carbpol.2015.04.040","article-title":"Carboxymethyl chitosan represses tumor angiogenesis in vitro and in vivo","volume":"129","author":"Jiang","year":"2015","journal-title":"Carbohydr. Polym."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"439","DOI":"10.2983\/035.028.0303","article-title":"Seasonal variation of physiological parameters in the eastern oyster crassostrea virginica from a tropical region of the gulf of Mexico","volume":"28","author":"Gullian","year":"2017","journal-title":"J. Shellfish Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1159\/000470896","article-title":"Use of an osteoblast overload damage model to probe the effect of icariin on the proliferation, differentiation and mineralization of mc3t3-e1 cells through the wnt\/\u03b2-catenin signalling pathway","volume":"41","author":"Liu","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.3892\/mmr.2016.5381","article-title":"Secretory leukocyte protease inhibitor promotes differentiation and mineralization of mc3t3-e1 preosteoblasts on a titanium surface","volume":"14","author":"Choi","year":"2016","journal-title":"Mol. Med. Rep."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/9\/2302\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:19:36Z","timestamp":1760195976000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/9\/2302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,9]]},"references-count":44,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["molecules23092302"],"URL":"https:\/\/doi.org\/10.3390\/molecules23092302","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,9]]}}}