title: Effect of glucosamine, a therapeutic agent for osteoarthritis, on osteoblastic cell differentiation.
abstract: Osteoarthritis (OA) is characterized by qualitative and quantitative changes in the architecture and composition of all the joint structures. Glucosamine (GlcN) has been used to treat OA in humans, because GlcN is present in the cartilage tissues as a component of glycosaminoglycans, and exhibits the symptom-modifying effect on OA by normalizing cartilage metabolism. On the other hand, the pathological change of subchondral bone is associated with the initiation and progression of cartilage damage in OA. However, the effect of GlcN on bone metabolism remains unsolved. In the present study, we determined the effect of GlcN on bone metabolism (osteoblastic cell differentiation) using mouse osteoblastic MC3T3-E1 cells by evaluating the expression of early (type I collagen and alkaline phosphatase), middle (osteopontin) and late (osteocalcin and mineralization) stage differentiation markers, and further compared its effects to those of N-acetyl-D-glucosamine (GlcNAc), a derivative of GlcN. The results indicated that the mineralization of mature osteoblasts was increased by treatment with GlcN and GlcNAc. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) analyses revealed that GlcN and GlcNAc substantially increased the expression of a middle stage marker and a late stage marker, although they did not essentially affect the expression of early stage markers. In addition, GlcN and GlcNAc suppressed the expression of receptor activator of NF-κB ligand (RANKL), a key factor involved in the osteoclastic cell differentiation and activation. Together these observations suggest that both GlcN and GlcNAc may have a potential not only to induce osteoblastic cell differentiation especially at middle-late stages, but also to suppress the osteoclastic cell differentiation, thereby possibly increasing bone matrix deposition and decreasing bone resorption, and eventually modulating bone metabolism in OA.
authors.affiliation: Department of Host Defense and Biochemical Research, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Igarashi
authors.forename: Koji
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Isao
authors.initials: I
authors.lastname: Nagaoka
mesh_terms: D000117:Acetylglucosamine / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism; D005944:Glucosamine / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism; D051379:Mice; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D024042:Collagen Type I; D006025:Glycosaminoglycans; D053246:Receptor Activator of Nuclear Factor-kappa B; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D005944:Glucosamine; D000117:Acetylglucosamine