Osteocyte Protein Expression Is Altered in Low-Turnover Osteoporosis Caused by Mutations in WNT1 and PLS3.

Abstract

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.

• Authors: Katherine Wesseling-Perry, Riikka E Mäkitie, Ville-Valtteri Välimäki, Tero Laine, Christine M Laine, Matti J Välimäki, Renata C Pereira, Outi Mäkitie
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 102 Issue 7 Pg. 2340-2348 (07 01 2017) ISSN: 1945-7197 [Electronic] United States
• PMID: 28379384 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2017 Endocrine Society

Chemical References

• FGF23 protein, human
• Membrane Glycoproteins
• Microfilament Proteins
• WNT1 protein, human
• Wnt1 Protein
• plastin
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23

Topics

• Adolescent
• Adult
• Aged
• Biopsy, Needle
• Bone Density (genetics)
• Bone Remodeling (genetics)
• Bone and Bones (pathology)
• Cells, Cultured
• Cohort Studies
• Cross-Sectional Studies
• Female
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (genetics)
• Gene Expression Regulation
• Hospitals, University
• Humans
• Ilium (metabolism, pathology)
• Immunohistochemistry
• In Situ Nick-End Labeling
• Male
• Membrane Glycoproteins (genetics)
• Microfilament Proteins (genetics)
• Middle Aged
• Mutation
• Osteocytes (metabolism)
• Osteoporosis (genetics, physiopathology)
• Signal Transduction
• Wnt1 Protein (genetics)
• Young Adult