title: Aquaporin 3 protects against lumbar intervertebral disc degeneration via the Wnt/β-catenin pathway.
abstract: Previous studies have demonstrated that the expression of aquaporin 3 (AQP3), a water channel which promotes glycerol permeability and water transport across cell membranes, is reduced in degenerative lumbar intervertebral disc (IVD) tissues. However, the role of AQP3 in the pathogenesis of IVD degeneration has not recieved much scholarly attention. The objective of the present study was to investigate the effect of AQP3 on cell proliferation and extracellular matrix (ECM) degradation in human nucleus pulposus cells (hNPCs) using gain-of-function and loss-of-function experiments, and to determine whether Wnt/β-catenin signaling is involved in the effect of AQP3 on IVD degeneration. hNPCs were transfected with the AQP3-pcDNA3.1 plasmid or AQP3 siRNA to overexpress or suppress AQP3. An MTT assay was performed to determine cell proliferation, and we found that AQP3 promoted hNPC proliferation. The expression of aggrecan, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4 and ADAMTS5 was detected using western blot analysis, to examine the effect of AQP3 on ECM degradation in hNPCs. The results revealed that AQP3 inhibited ECM degradation in hNPCs. In addition, we found that Wnt/β-catenin signaling was suppressed by AQP3. However, the effect of AQP3 on hNPC proliferation and ECM degradation was reversed by treatment with lithium chloride, a known activator of Wnt/β‑catenin signaling. In conclusion, using in vitro and in vivo tests, we have reported for the first time, to the best of our knowledge, that AQP3 exerts protective effects against IVD degeneration, and these are effected, at least partially, through the inhibition of Wnt/β-catenin signaling.
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Huanxin
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Jingjun
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Xintao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Changcheng
authors.initials: C
authors.lastname: You
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Jinglong
authors.initials: J
authors.lastname: Yan
mesh_terms: D051400:Aquaporin 3 / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000378:metabolism* / Q000517:prevention & control; D000070614:Nucleus Pulposus / Q000166:cytology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin; D051400:Aquaporin 3