Osteocyte protein expression is altered in low-turnover osteoporosis caused by mutations in WNT1 and PLS3.

Osteocyte protein expression is altered in low-turnover osteoporosis caused by mutations in WNT1 and PLS3.

J Clin Endocrinol Metab. 2017 Apr 03;:

Authors: Wesseling-Perry K, Mäkitie RE, Välimäki VV, Laine T, Laine CM, Välimäki MJ, Pereira RC, Mäkitie O

Abstract
Context: Osteocytes express proteins that regulate bone remodeling and mineralization as well as osteoblast and adipocyte differentiation.
Objective: To evaluate the relationship between osteocyte-specific protein expression and bone histology in patients with monogenic osteoporosis due to WNT1 or PLS3 mutations.
Design and Setting: Cross-sectional cohort study at a University Hospital.
Participants: 6 patients (4 males, age range 14-72 years) with a heterozygous WNT1 mutation and 5 patients (4 males, age 9-70 years) with a hetero-/hemizygous PLS3 mutation.
Methods and Main Outcome Measures: Immunohistochemistry was performed for FGF23, DMP1, sclerostin, and phosphor-β-catenin in iliac crest samples and compared to histomorophometric parameters of bone turnover, mineralization, volume, and adiposity.
Results: FGF23 expression in WNT1 patients was 243% that observed in PLS3 patients (p<0.01). DMP1, sclerostin, and phosphor-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). Phosphor-β-catenin expression correlated inversely with trabecular 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). Trabecular FGF23 expression did not correlate with trabecular DMP1 expression, cortical sclerostin expression, or any histomorphometric parameter. Marrow adiposity was higher in WNT1 than in PLS3 patients (p=0.04). Adipocyte number did not correlate with cortical sclerostin or phosphor-β-catenin expression.
Conclusions: Specific mutations that disrupt WNT signaling and osteocytic mechano-sensing affect osteocyte protein expression. Abnormal osteocyte function may play a role in the pathogenesis of monogenetic forms of osteoporosis.

PMID: 28379384 [PubMed - as supplied by publisher]

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