ArticleNature biomedical engineering2026
Sulfated polysaccharides target RANK Lys97 to inhibit osteoclast differentiation and reverse osteoporosis.
Article in Nature biomedical engineering, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
6 authors.
Funding
Abstract
Current osteoporosis treatments fail to balance bone resorption and formation. Here we show that engineered 2-N,6-O-sulfated chitosan (26SCS), a synthetic pentasaccharide, restores 115% bone mass (therapeutic) and prevents 66% bone loss, surpassing bisphosphonates by simultaneously suppressing osteoclastogenesis and promoting vascularized osteogenesis. Mechanistically, 26SCS targets K97 in receptor activator of nuclear factor-κB (RANK) through geometrically matched sulfate pairs, blocking RANK ligand (RANKL) signalling to arrest preosteoclast fusion while enhancing platelet-derived growth factor-BB (PDGF-BB) secretion via preserved preosteoclast viability to drive angiogenesis-coupled mineralization. Structural and functional analyses reveal that carboxyl groups in natural glycosaminoglycans such as heparin competitively bind K97, disrupting therapeutic specificity-a limitation overcome by 26SCS's carboxyl-free design and sequence-controlled sulfation. Unlike monosulfated analogues (2SCS/6SCS) that oversuppress osteoclastogenesis or lack pro-osteogenic effects, 26SCS's dual sulfation balances inhibition with trophic support. Thus, this work redefines glycosaminoglycan therapeutics via sulfation-patterned, topology-engineered biomaterials harmonizing bone metabolism.
Identifiers
42533072What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.