title: Local delivery of a carbohydrate analog for reducing arthritic inflammation and rebuilding cartilage.
abstract: Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation. Because OA has a multifactorial nature and complex interrelationship of the individual elements of a whole joint, there is a need for comprehensive therapeutic approaches for cartilage tissue engineering, which simultaneously address multiple aspects of disease etiology. In this work, we investigated a multifunctional carbohydrate-based drug candidate, tri-butanoylated N-acetyl-D-galactosamine analog (3,4,6-O-Bu3GalNAc) that induced cartilage tissue production by human mesenchymal stem cells (hMSCs) and human OA chondrocytes by modulating Wnt/β-catenin signaling activity. The dual effects promoted chondrogenesis of human MSC and reduced inflammation of human OA chondrocytes in in vitro cultures. Translating these findings in vivo, we evaluated therapeutic effect of 3,4,6-O-Bu3GalNAc on the rat model of posttraumatic OA when delivered via local intra-articular sustained-release delivery using microparticles and found this method to be efficacious in preventing OA progression. These results show that 3,4,6-O-Bu3GalNAc, a disease modifying OA drug candidate, has promising therapeutic potential for articular cartilage repair.
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
authors.forename: Chaekyu
authors.initials: C
authors.lastname: Kim
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
authors.forename: Ok Hee
authors.initials: OH
authors.lastname: Jeon
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
authors.forename: Do Hun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
authors.forename: J Jeremy
authors.initials: JJ
authors.lastname: Chae
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
authors.forename: Lucas
authors.initials: L
authors.lastname: Shores
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bernstein
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Bhattacharya
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
authors.forename: Jeannine M
authors.initials: JM
authors.lastname: Coburn
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Yarema
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA. Electronic address: jhe@jhu.edu.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Elisseeff
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020219:Chondrogenesis / Q000187:drug effects; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005688:Galactosamine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010003:Osteoarthritis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D005688:Galactosamine
keywords: Carbohydrates; Disease-modifying OA drug; Drug delivery; Mesenchymal stem cells; Osteoarthritis; Tissue engineering