title: Osteocyte Protein Expression Is Altered in Low-Turnover Osteoporosis Caused by Mutations in WNT1 and PLS3.
abstract: Osteocytes express proteins that regulate bone remodeling and mineralization.
  
  
  
  To evaluate the relationship between osteocyte-specific protein expression and bone histology in patients with monogenic osteoporosis due to wingless integration site 1 (WNT1) or plastin 3 (PLS3) mutations.
  
  
  
  Cross-sectional cohort study at a university hospital.
  
  
  
  Six patients (four males; ages: 14 to 72 years) with a heterozygous WNT1 mutation and five patients (four males; ages: 9 to 70 years) with a heterozygous/hemizygous PLS3 mutation.
  
  
  
  Immunohistochemistry was performed for fibroblast growth factor 23 (FGF23), dentin matrix protein 1 (DMP1), sclerostin, and phosphorylated (phospho-)β-catenin in iliac crest samples and compared with bone histomorphometry.
  
  
  
  FGF23 expression in WNT1 patients was 243% that observed in PLS3 patients (P < 0.01). DMP1, sclerostin, and phospho-β-catenin expression did not differ between groups. Serum phosphate correlated inversely with FGF23 expression (r = -0.79, P = 0.01) and serum ionized calcium correlated inversely with sclerostin expression (r = -0.60, P = 0.05). Phospho-β-catenin expression correlated inversely with DMP1 expression (r = -0.88, P < 0.001), osteoid volume/bone volume (r = -0.68, P = 0.02), and bone formation rate (r = -0.78, P < 0.01). FGF23 expression did not correlate with DMP1 expression, sclerostin expression, or bone histomorphometry. Marrow adiposity was higher in WNT1 than in PLS3 patients (P = 0.04).
  
  
  
  Mutations that disrupt WNT signaling and osteocytic mechanosensing affect osteocyte protein expression. Abnormal osteocyte function may play a role in the pathogenesis of monogenetic forms of osteoporosis.
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095.
authors.forename: Katherine
authors.initials: K
authors.lastname: Wesseling-Perry
authors.affiliation: Folkhälsan Institute of Genetics, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Riikka E
authors.initials: RE
authors.lastname: Mäkitie
authors.affiliation: Department of Orthopedics and Traumatology, Helsinki University Central Hospital and Helsinki University, Jorvi Hospital, 02740 Espoo, Finland.
authors.forename: Ville-Valtteri
authors.initials: VV
authors.lastname: Välimäki
authors.affiliation: Department of Orthopedics, Institute of Clinical Sciences, Sahlgrenska University Hospital and University of Gothenburg, 41345 Gothenburg, Sweden.
authors.forename: Tero
authors.initials: T
authors.lastname: Laine
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland.|Department of Endocrinology, Institute of Medicine, Sahlgrenska University Hospital and University of Gothenburg, 41345 Gothenburg, Sweden.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Laine
authors.affiliation: Division of Endocrinology, Department of Medicine, Helsinki University Central Hospital, 00029 Helsinki, Finland.
authors.forename: Matti J
authors.initials: MJ
authors.lastname: Välimäki
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095.
authors.forename: Renata C
authors.initials: RC
authors.lastname: Pereira
authors.affiliation: Folkhälsan Institute of Genetics, University of Helsinki, 00014 Helsinki, Finland.|Children's Hospital, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland.|Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden.|Department of Clinical Genetics, Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Outi
authors.initials: O
authors.lastname: Mäkitie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D015519:Bone Density / Q000235:genetics; D016723:Bone Remodeling / Q000235:genetics; D001842:Bone and Bones / Q000473:pathology; D002478:Cells, Cultured; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics*; D005786:Gene Expression Regulation; D006785:Hospitals, University; D006801:Humans; D007085:Ilium / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010011:Osteocytes / Q000378:metabolism; D010024:Osteoporosis / Q000235:genetics* / Q000503:physiopathology; D015398:Signal Transduction; D051155:Wnt1 Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: C000717427:FGF23 protein, human; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; C495247:WNT1 protein, human; D051155:Wnt1 Protein; C026742:plastin; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23