MicroRNAs (miRNAs) regulate gene expression post‐transcriptionally and circulate in the blood, making them attractive biomarkers of disease state for tissues like bone that are challenging to interrogate directly. Here, we report on five miRNAs—miR‐197‐3p, miR‐320a, miR‐320b, miR‐331‐5p, and miR‐423‐5p—associated with bone mineral density (BMD) in 147 healthy adult baboons. These baboons ranged in age from 15 to 25 years (45–75 human equivalent years) and 65% were female with a broad range of BMD values including a minority of osteopenic animals. miRNAs were generated via RNA sequencing from buffy coats collected at necropsy and areal BMD (aBMD) measured postmortem via dual‐energy X‐ray absorptiometry (DXA) of the lumbar vertebrae. Differential expression analysis controlled for the underlying pedigree structure of these animals to account for genetic variation which may drive miRNA abundance and aBMD values. While many of these miRNAs have been associated with the risk of osteoporosis in humans, this finding is of interest because the cohort represents a model of normal aging and bone metabolism rather than a disease cohort. The replication of miRNA associations with osteoporosis or other bone metabolic disorders in animals with healthy aBMD suggests an overlap in normal variation and disease states. We suggest that these miRNAs are involved in the regulation of cellular proliferation, apoptosis, and protein composition in the extracellular matrix throughout life; and age‐related dysregulation of these systems may lead to disease. These miRNAs may be early indicators of progression to disease in advance of clinically detectible osteoporosis.
Aims: Ectopic fat is a recognized contributor to insulin resistance and metabolic dysfunction, while the role of fat deposition inside intestinal wall tissue remains understudied. We undertook this study to directly quantify and localize intramural fat deposition in duodenal tissue and determine its association with adiposity.
MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and circulate in the blood, making them attractive biomarkers of disease state for tissues like bone that are challenging to interrogate directly. Here we report on five miRNAs - miR-197-3p, miR-320a, miR-320b, miR-331-5p, and miR-423-5p - that are associated with bone mineral density (BMD) in 147 healthy adult baboons. These baboons range in age from 15 to 25 years (45 to 75 human equivalent years) and were 65% female with a broad range of BMDs including a minority of osteopenic individuals. miRNAs were generated via RNA sequencing from buffy coats collected at necropsy and areal BMD evaluated via DXA of the lumbar vertebrae post-mortem. Differential expression analysis controlled for the underlying pedigree structure of these animals to account for genetic variation which may be driving miRNA abundance and BMD values. While many of these miRNAs have been associated with risk of human osteoporosis, this finding is of interest because the cohort represent a model of normal aging and bone metabolism rather than a disease cohort. The replication of miRNA associations with osteoporosis or other bone metabolic disorders in animals with healthy BMD suggests an overlap in normal variation and disease states. We suggest that these miRNAs are involved in the regulation of cellular proliferation, apoptosis, and protein composition in the extracellular matrix throughout life. However, age-related dysregulation of these systems may lead to disease causing associations of the miRNAs among individuals with clinically defined disease.
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