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Current treatments offer short\u2010term benefits but are limited by long\u2010term efficacy and adverse effects, highlighting the need for new strategies. Chondroitin sulfate polysaccharides (CS), a major component of the bone matrix, are crucial for bone and cartilage health. However, their role in osteoporosis is understudied due to the heterogeneity of natural CS. we found reduced CS levels in osteoporosis patients and developed CS4\u2010NP, a self\u2010assembled tetrasaccharide nanoparticle that mimics CS's structure. CS4\u2010NP, which efficiently delivers the active CS4, significantly improves bone mass in ovariectomized osteoporosis models. It activates the Activating Transcription Factor 4\u2010Cystathionine gamma\u2010Lyase signaling axis in pre\u2010osteoblasts, enhancing osteogenesis. our findings suggest that CS4\u2010NP, an oligosaccharide\u2010based nanomaterial, could address the limitations of current treatments and provide a viable strategy for osteoporosis.<\/jats:p>","DOI":"10.1002\/adhm.202402976","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:09:10Z","timestamp":1733098150000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Self\u2010Assembled Nanoparticles with Well\u2010Defined Oligosaccharide Promote Osteogenesis by Regulating Golgi Stress Response"],"prefix":"10.1002","volume":"14","author":[{"given":"Pingping","family":"Niu","sequence":"first","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; Tongji Research Institute of Stomatology 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