title: Glucosamine regulates differentiation of a chondrogenic cell line, ATDC5.
abstract: Osteoarthritis (OA) is a slowly progressing chronic joint disease. Glucosamine (GlcN) is a saccharide that is widely used to relieve symptoms associated with OA. However, the mechanism of the effects of GlcN on articular cartilage remains unclear. We studied the effects of GlcN and its analogues, including chitin derivatives included in health supplements containing GlcN, on a chondrogenic cell line, ATDC5. We examined the effects of these saccharides on the proliferation and differentiation of ATDC5 cells. Glucosamine analogues, such as N-acetyl glucosamine and chitobiose, did not affect the proliferation or differentiation of ATDC5 cells. While GlcN did not affect the proliferation of ATDC5 cells, it inhibited their differentiation. Next, we examined whether GlcN affects mineralization and glycosaminoglycan (GAG) production by ATDC5 cells. Mineralization was markedly inhibited by addition of GlcN to the cell culture medium. Moreover, GlcN induced the formation of sulfated GAG in ATDC5. We also analyzed the mRNA levels in ATDC5 cells. GlcN reduced the mRNA levels of Smad2, Smad4 and MGP. GlcN might inhibit expression of MGP mRNA and induce the production of chondroitin sulfate in ATDC5 cells. The mechanism by which GlcN inhibits mineralization may be by regulating the expression of mRNA for the Smad2 and Smad4 chondrogenic master genes.
authors.affiliation: Department of Food Functional Science, Graduate School of Pharmacology, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0248, Japan.
authors.forename: Sachie
authors.initials: S
authors.lastname: Nakatani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mano
authors.forename: Ryanghyok
authors.initials: R
authors.lastname: Im
authors.forename: Jun
authors.initials: J
authors.lastname: Shimizu
authors.forename: Masahiro
authors.initials: M
authors.lastname: Wada
mesh_terms: D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors; D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002356:Cartilage / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D005944:Glucosamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism; D000097568:Matrix Gla Protein
chemical_list: D000469:Alkaline Phosphatase; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D005944:Glucosamine; D006025:Glycosaminoglycans; D012333:RNA, Messenger; D051899:Smad2 Protein; D051901:Smad4 Protein; D013431:Sulfates; D000097568:Matrix Gla Protein