Impaired osteogenesis in Menkes disease-derived induced pluripotent stem cells

Stem Cell Research & Therapy
Dongkyu KimYong-Mahn Han

Abstract

Bone abnormalities, one of the primary manifestations of Menkes disease (MD), include a weakened bone matrix and low mineral density. However, the molecular and cellular mechanisms underlying these bone defects are poorly understood. We present in vitro modeling for impaired osteogenesis in MD using human induced pluripotent stem cells (iPSCs) with a mutated ATP7A gene. MD-iPSC lines were generated from two patients harboring different mutations. The MD-iPSCs showed a remarkable retardation in CD105 expression with morphological anomalies during development to mesenchymal stem cells (MSCs) compared with wild-type (WT)-iPSCs. Interestingly, although prolonged culture enhanced CD105 expression, mature MD-MSCs presented with low alkaline phosphatase activity, reduced calcium deposition in the extracellular matrix, and downregulated osteoblast-specific genes during osteoblast differentiation in vitro. Knockdown of ATP7A also impaired osteogenesis in WT-MSCs. Lysyl oxidase activity was also decreased in MD-MSCs during osteoblast differentiation. Our findings indicate that ATP7A dysfunction contributes to retardation in MSC development and impairs osteogenesis in MD.

References

May 20, 1972·Lancet·D M DanksB Turner
Mar 1, 1982·The Journal of Clinical Investigation·H KuivaniemiK I Kivirikko
Oct 1, 1993·European Journal of Pediatrics·J KreuderD Dralle
Apr 1, 1997·Journal of Medical Genetics·Z Tümer, N Horn
May 20, 1998·The American Journal of Clinical Nutrition·J F Mercer
May 20, 1998·The American Journal of Clinical Nutrition·S G Kaler
Aug 27, 1999·Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society·S G Kaler
Jul 12, 2002·Medical Electron Microscopy : Official Journal of the Clinical Electron Microscopy Society of Japan·Hitohiko MurakamiNorimichi Nemoto
Nov 1, 2002·Journal of Inherited Metabolic Disease·S KanumakalaM Zacharin
Dec 17, 2002·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Marie-Cécile NassogneJean-Marie Saudubray
Feb 11, 2003·Journal of Cellular Biochemistry·Herbert M Kagan, Wande Li
Dec 1, 2005·The Journal of Nutrition·Jean-François MontyDavid R Kramer
Aug 16, 2006·Cellular and Molecular Life Sciences : CMLS·H A Lucero, H M Kagan
Aug 31, 2006·The Journal of Pediatrics·Sarah C GodwinStephen G Kaler
Nov 3, 2006·Cancer Research·Janine T Erler, Amato J Giaccia
Nov 30, 2006·Journal of Cellular Biochemistry·Charles A GersbachAndrés J García
May 29, 2007·Archives of Biochemistry and Biophysics·Sharon La Fontaine, Julian F B Mercer
Jul 7, 2007·Physiological Reviews·Svetlana LutsenkoOleg Y Dmitriev
May 13, 2008·Cardiovascular Research·Cristina RodríguezLina Badimon
Oct 24, 2009·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Amanda N BarrySvetlana Lutsenko
Feb 25, 2010·Pediatric Radiology·Eva AmadorGoya Enríquez
Mar 5, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Amer MahmoodMoustapha Kassem
Jan 12, 2011·Nature Reviews. Neurology·Stephen G Kaler
Feb 2, 2011·Journal of the National Cancer Institute·Ann-Marie BakerJanine T Erler
Nov 1, 2011·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Yves MauryCécile Martinat
Nov 15, 2011·Current Biology : CB·Richard A Festa, Dennis J Thiele
Nov 15, 2011·Nature Reviews. Drug Discovery·Marica GrskovicGeorge Q Daley
Jan 24, 2012·Orphanet Journal of Rare Diseases·Lisbeth Birk MøllerThomas G Jensen
Jul 7, 2012·Biochemical and Biophysical Research Communications·Hyemin KimYong-Mahn Han

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Citations

Jan 26, 2016·International Journal of Molecular Sciences·Siddharth MenonNatalina Quarto
Mar 21, 2017·Pediatric Dermatology·Rebecca J DromsKaren Wiss
Dec 2, 2017·International Journal of Molecular Sciences·Jung-Yun ChoiYong-Mahn Han
Nov 21, 2018·Journal of Drug Targeting·Lijun ChenWande Li
May 18, 2021·Pediatric Radiology·Jai SidpraKshitij Mankad

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Methods Mentioned

BETA
transfection
PCR
electrophoresis
FACS
protein assay

Software Mentioned

QUMA
FlowJo

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