Circulating miRNAs associated with bone mineral density in healthy adult baboons

Details

• Alternative Title:
  J Orthop Res
• Personal Author:
  Quillen, Ellen. E. ; Foster, Jaydee ; Sheldrake, Anne ; Stainback, Maggie ; Glenn, Jeremy ; Cox, Laura A. ; Bredbenner, Todd L.
• Description:
  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.
• Subjects:
  Aging Animals Article Bone Density Bone Mineral Density Circulating MicroRNA Female Humans Male MicroRNAs MiRNA Non-human Primate Osteoporosis Papio

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• Source:
  J Orthop Res. 40(8):1827-1833
• Pubmed ID:
  34799865
• Pubmed Central ID:
  PMC9117570
• Document Type:
  Journal Article
• Funding:
  K01 AG056663/AG/NIA NIH HHSUnited States/ ; P51 OD011133/OD/NIH HHSUnited States/ ; R01 AR064244/AR/NIAMS NIH HHSUnited States/ ; P51 OD011133/CD/ODCDC CDC HHSUnited States/
• Volume:
  40
• Issue:
  8
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:9d23e656678053840523a185aaf4e11558d5556f18ceddd071f1f87cd5b392e9
• Download URL:
  https://stacks.cdc.gov/view/cdc/117642/cdc_117642_DS1.pdf
• File Type:
  [PDF - 1.65 MB ]