Researchers have identified miR-34a as a promising molecule that blocks bone destruction, according to a study published online ahead of print June 25 in Nature. Lead study author Yihong Wan, PhD, Assistant Professor of Pharmacology and member of the UT Southwestern Harold C. Simmons Cancer Center, and her research colleagues reported that mice with higher than normal levels of miR-34a had increased bone mass and reduced bone breakdown. According to the researchers, this is because miR-34a blocks osteoclasts, which make the bone less dense and prone to fracture.
“This new finding may lead to the development of miR-34a mimics as a new and better treatment for osteoporosis and cancers that metastasize to the bone,” said Dr. Wan.
Investigators found that injecting nanoparticles containing a mimic, or artificial version of miR-34a, into a mouse with post-menopausal osteoporosis decreased bone loss. miR-34a could also offer protection from bone metastases in a variety of cancers, Dr. Wan noted. Injecting the miR-34a mimic in the mice could prevent the metastasis of skin and breast cancer because it can disarm the metastatic niche in bone.
Study findings also suggest:
• MicroRNAs play important roles in physiology and disease, and present tremendous therapeutic potential.
• miR-34a is downregulated during osteoclast differentiation.
• Osteoclastic miR-34a-overexpressing transgenic mice exhibit lower bone resorption and higher bone mass.
• miR-34a knockout and heterozygous mice exhibit elevated bone resorption and reduced bone mass.
• Ovariectomy-induced osteoporosis, as well as bone metastasis of breast and skin cancers, are diminished in osteoclastic miR-34a transgenic mice, and can be effectively attenuated by miR-34a nanoparticle treatment.
• Transforming growth factor-β-induced factor 2 (Tgif2) as an essential direct miR-34a target that is pro-osteoclastogenic.
• Tgif2 deletion reduces bone resorption and abolishes miR-34a regulation.
Commenting on the study findings Dr. Wan said, “The mouse miR-34a is identical to that in humans, which means that our findings may apply to humans as well.”