Far from being “micro” news, a new research endeavor from the laboratory of Dr. Yihong Wan at UT Southwestern could be the next breakthrough in treating osteoporosis and bone metastases of cancer. Dr. Wan’s research group found that miR-34a, a member of the microRNA family, increases bone mass and reduces bone breakdown.
The findings were reported online in Nature and were made through a few ex vivo experiments and mouse models, although the sequence is conserved between mice and humans. “Interestingly, the mouse miR-34a is identical to that in humans, which means that our findings may apply to humans as well,” said Dr. Wan in a news release.
In mice that had over-expression of miR-34a in osteoclasts (bone resorbing cells), lower levels of resorption markers were observed due to fewer differentiated osteoclasts. This directly translated into increased bone mass. Conversely, when mice without miR-34a were generated, osteoclast differentiation was increased and resorption markers were elevated.
To make the study more clinically relevant, Dr. Wan’s team generated osteoporotic mice through an ovariectomy and injected the mice with artificial miR-34a loaded in chitosan nanoparticles. The nanoparticles accumulated mostly in the bone marrow, where osteoclast precursors develop, and attenuated ovariectomy-induced bone loss. Non-ovariectomized mice also saw an increase in bone mass after nanoparticle injection.
Interested in more than treating osteoporosis, the group investigated the effects of miR-34a on bone metastases, which result from, for example, breast or skin cancers traveling to bone and establishing a new cancer location. miRNA injections dismantled the metastatic niche in bone, thereby preventing potential metastases in bone.
“We were very excited to see, through this collaborative work with Dr. Wan’s group, that miR-34a can also suppress bone metastasis. Thus, miR-34a-based therapy could provide multiple benefits for cancer patients,” said Dr. Joshua Mendell, who is a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar in Cancer Research. Dr. Mendell previously identified cancer cell growth suppression by miR-34a and is Professor of Molecular Biology at UT Southwestern.
Rounding out the group were Drs. Xian-Jin Xie and Tsung-Cheng Chang and postdoctoral researchers Jing Krzeszinski, Wei Wei, HoangDinh Huynh, Zixue Jin, and Xunde Wang. Lin He from UC Berkeley and Lingegowda Mangala, Gabriel Lopez-Berestein, and Anil Sood from UT MD Anderson Cancer Center were also collaborators. Together, they are helping to solve the problem of osteoporosis, which affects mainly seniors and women and causes more than 1.5 million fractures a year.