title: Effects of a glycogen synthase kinase-3β inhibitor (LiCl) on c-myc protein in intervertebral disc cells.
abstract: Wnt/β-catenin (hereafter called Wnt) signaling is a key inducer and regulator of joint development, and is involved in the formation of bone and cartilage. We previously reported that Wnt signaling plays an essential role in the control of cell proliferation and cell senescence in intervertebral disc cells. In the present study, we provide evidence that the expression of c-myc, a key protein required for cell proliferation, is regulated by Wnt signaling. Our data also show that activation of Wnt signaling by LiCl, a Wnt signaling activator, leads to the suppression of c-myc promoter activity and expression. To ascertain whether Wnt signaling regulates the expression of c-myc, we measured both its transcript and protein expression. Following treatment with LiCl, c-myc expression was suppressed at both the mRNA and protein levels. In nucleus pulposus cells treated with c-myc, cell viability increased significantly, whereas treatment with a c-myc inhibitor decreased cell viability. Taken together, these results suggest that c-myc is an important factor that promotes the proliferation of nucleus pulposus cells. These findings provide new insight into the regulation and maintenance of cell proliferation in nucleus pulposus cells.
authors.affiliation: Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan. a.hiyama@tokai-u.jp
authors.forename: Akihiko
authors.initials: A
authors.lastname: Hiyama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sakai
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Arai
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakajima
authors.forename: Katsuya
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Joji
authors.initials: J
authors.lastname: Mochida
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000166:cytology* / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D051153:Wnt Proteins; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride