MicroRNA-467g inhibits new bone regeneration by targeting Ihh/Runx-2 signaling.
MicroRNAs are important post transcriptional regulators of gene expression and play critical role in osteoblast differentiation. In this study we report miR-467g, an uncharacterized novel miRNA, in regulation of osteoblast functions. Over-expression of miR-467g inhibited osteoblast differentiation. Target prediction analysis tools and experimental validation by luciferase 3' UTR reporter assay identified Runx-2 as a direct target of miR-467g. Over expression of miR-467g in osteoblasts down regulated Runx-2 and Ihh signaling components. Furthermore, silencing of miR-467g was done to see its role in Ihh and Runx-2 mediated bone healing and regeneration in a drill hole injury model in BALB/c mice. Silencing of miR-467g led to significant increase in new bone regeneration and Ihh and Runx-2 localization at injury site in a day dependent manner. In conclusion, miR-467g negatively regulates osteogenesis by targeting Ihh/Runx-2 signaling. We, thus, propose that therapeutic approaches targeting miR-467g could be useful in enhancing the new bone formation.
Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Lucknow, India.
Jyoti
J
Kureel
Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Lucknow, India.
Aijaz A
AA
John
Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Lucknow, India.
Manisha
M
Dixit
Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Lucknow, India. Electronic address: divya_singh@cdri.res.in.
Divya
D
Singh
D000818:Animals; D001861:Bone Regeneration / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D010006:Osteoblasts / Q000166:cytology; D015398:Signal Transduction / Q000235:genetics*
D050659:Core Binding Factor Alpha 1 Subunit; D053823:Hedgehog Proteins; D035683:MicroRNAs; C514061:ihh protein, mouse
Hedgehog signaling; MicroRNA; Osteoblast differentiation; Runx-2; bone regeneration; osteogenesis