title: In vitro osteogenic differentiation is affected in Wiedemann-Rautenstrauch-Syndrome (WRS).
abstract: BACKGROUND
  Wiedemann-Rautenstrauch (neonatal progeroid) syndrome (WRS) is a rare autosomal recessive condition, with the characteristic appearance of premature aging already present at birth and other typical features (hypotrichosis, macrocephaly, mental retardation, aged face, generalized lipoatrophy, abnormal tooth status, osteopenia and other skeletal abnormalities). To date, there are no data about the differentiation capacity of WRS progenitor cells available in the literature.
  
  
  METHODS
  To elucidate the osteoblastic and chondroblastic regeneration potential in WRS, a progenitor cell culture system was used. Bone marrow-derived stem cells of a 16-year-old WRS patient were cultivated and stimulated by dexamethasone, ascorbic acid and beta-glycerolphosphate (DAG) over 21 days. Immunocytochemical stainings of CD34, CD45, CD105, osteocalcin, osteopontin and collagen II served for a quantitative evaluation of the differentiated cells. The results were compared to bone marrow-derived stem cells of a healthy female volunteer donor.
  
  
  RESULTS
  It was shown, for the first time, that WRS cells showed a highly significant lower in vitro response to osteoblastic differentiation stimulus. Furthermore, significantly fewer chondrocytes and hematopoietic cells were induced in WRS progenitors compared to the control group.
  
  
  CONCLUSIONS
  Our data suggest a lack of cellular differentiation capacity in WRS patients, which may be responsible for the clinical appearance and symptoms of this rare disorder.
authors.affiliation: Orthopaedic Research Laboratory, Department of Orthopaedics, Heinrich-Heine University Duesseldorf Moorenstr. 5, D-40225 Duesseldorf, Germany. Jaeger@med.uni-duesseldorf.de
authors.forename: Marcus
authors.initials: M
authors.lastname: Jäger
authors.forename: Fritz
authors.initials: F
authors.lastname: Thorey
authors.forename: Bettina
authors.initials: B
authors.lastname: Westhoff
authors.forename: Alexander
authors.initials: A
authors.lastname: Wild
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Krauspe
mesh_terms: D000293:Adolescent; D019588:Aging, Premature / Q000175:diagnosis; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000096:biosynthesis; D001205:Ascorbic Acid / Q000494:pharmacology; D001851:Bone Diseases, Metabolic / Q000000981:diagnostic imaging; D001854:Bone Marrow Cells / Q000166:cytology; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D000071063:Endoglin; D019066:Facies; D005260:Female; D005808:Genes, Recessive; D005994:Glycerophosphates / Q000737:chemistry; D006412:Hematopoietic Stem Cells; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008607:Intellectual Disability / Q000175:diagnosis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects; D015675:Osteocalcin / Q000096:biosynthesis; D053495:Osteopontin; D011859:Radiography; D011956:Receptors, Cell Surface; D012600:Scoliosis / Q000175:diagnosis / Q000000981:diagnostic imaging*; D012795:Sialoglycoproteins / Q000096:biosynthesis; D013234:Stem Cells / Q000166:cytology; D013577:Syndrome; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D024043:Collagen Type II; C064206:ENG protein, human; D000071063:Endoglin; D005994:Glycerophosphates; D011956:Receptors, Cell Surface; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D019010:Vascular Cell Adhesion Molecule-1; D015675:Osteocalcin; D053495:Osteopontin; D003907:Dexamethasone; D017493:Leukocyte Common Antigens; D001205:Ascorbic Acid