Unique, gender ‐dependent serum microRNA profile in PLS3 gene‐related osteoporosis

ABSTRACTPlastin 3 (PLS3), encoded byPLS3, is a newly recognized regulator of bone metabolism and mutations in the encoding gene result in severe childhood ‐onset osteoporosis. Since an X chromosomal gene,PLS3 mutation ‐positive males are typically more severely affected while females portray normal to increased skeletal fragility. Despite the severe skeletal pathology, conventional metabolic bone markers tend to be normal and are thus insufficient in diagnosing or monitoring patients. Our study aimed to explore serum microRNA (miRNA) concentrations in subjects with defective PLS3 function to identify novel markers that could differentiate subjects according to mutation status and give insight into the molecular mechanisms by which PLS3 regulates skeletal health. We analyzed fasting serum samples for a cus tom‐designed panel comprising 192 miRNAs in 15 mutation‐positive (5 males, age range 8–76 years, median 41 years) and 14 mutation‐negative (6 males, 8–69 years, 40 years) subjects from four Finnish families with differentPLS3 mutations. We identified a unique miRNA expression profile in the mutation ‐positive subjects with seven significantly up‐ or downregulated miRNAs (miR‐93‐3p, miR‐532‐3p, miR‐133a‐3p, miR‐301b‐3p, miR‐181c‐5p, miR‐203a‐3p, miR‐590‐3p;p‐values 0.004–0.044). Surprisingly, gender subgroup analysis revealed the difference to be even more distinct in female mutation‐positive subjects (congruentp ‐...
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: Tags: Original Article Source Type: research