Osteocyte Protein Expression Is Altered in Low-Turnover Osteoporosis Caused by Mutations in WNT1 and PLS3
| Autor: | Renata C. Pereira, Ville-Valtteri Välimäki, Christine M. Laine, Tero Laine, Riikka E. Mäkitie, Outi Mäkitie, Katherine Wesseling-Perry, Matti Välimäki |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Fibroblast growth factor 23 Endocrinology Diabetes and Metabolism Clinical Biochemistry Osteoporosis Biochemistry Bone remodeling Cohort Studies Hospitals University chemistry.chemical_compound 0302 clinical medicine Endocrinology Bone Density Cells Cultured Membrane Glycoproteins Biopsy Needle Microfilament Proteins Middle Aged Immunohistochemistry medicine.anatomical_structure Osteocyte embryonic structures Female Bone Remodeling Signal Transduction Adult medicine.medical_specialty animal structures Adolescent 030209 endocrinology & metabolism Wnt1 Protein Osteocytes Bone and Bones Ilium Young Adult 03 medical and health sciences stomatognathic system Internal medicine In Situ Nick-End Labeling medicine PLS3 Humans Clinical Research Articles Aged business.industry Osteoid Biochemistry (medical) medicine.disease DMP1 Fibroblast Growth Factors stomatognathic diseases Fibroblast Growth Factor-23 Cross-Sectional Studies 030104 developmental biology Gene Expression Regulation chemistry Mutation Sclerostin business |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 102:2340-2348 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2017-00099 |
| Popis: | Context Osteocytes express proteins that regulate bone remodeling and mineralization. Objective 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. Design and Setting Cross-sectional cohort study at a university hospital. Participants 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. Methods and Main Outcome Measures 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. Results 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). Conclusions 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. |
| Databáze: | OpenAIRE |
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