MicroRNA, Angiogenesis and Skeletal Anabolic Response to Mechanical Strain
Abstract
Bone is a highly vascularized tissue reliant on the close spatial and temporal connection between blood vessels and bone cells to maintain skeletal integrity. Several experimental studies have shown that angiogenesis plays a vital role in skeletal development and bone fracture repair. 1) Studies using a distraction osteogenesis model (DO) have shown that intramembranous bone formation is induced by the application of gradual mechanical distraction across an osteotomy defect, which reveals not only an increase in osteogenesis but also an increase in expression of several angiogenic factors (1). 2) Treadmill-running in rats displayed bone marrow angiogenesis concomitant with increase in osteogenesis (2). 3) Studies using mandibular DO model have shown that high frequency traction provides a proper mechanical environment for angiogenesis contributing to enhanced bone formation (3). These findings illustrate that angiogenesis, osteogenesis and ML are tightly related. Recently, newly discovered MicroRNA (miR) s belonging to a small class of RNA molecules have received considerable attention because of the ability to act as a negative regulator of gene expression. So far, at least 500 MicroRNAs have been discovered of which few are linked to pathogenesis of disease (4-7). In particular, MicroRNA92a has been reported to control angiogenesis. Since angiogenesis and osteogenesis are critical for increasing bone healing and bone strength in the rehabilitation program, we predict that inhibiting miR that control angiogenesis can maximize the benefits of exercise on skeleton. Based on this and the above rationale, we propose the hypothesis that blocking miR that control angiogenesis will increase the magnitude of anabolic effects on ML on bone formation. To test this, two specific aims are proposed.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2013
- Accession Number
- ADA590547
Entities
People
- Chandrasekar Kesavan