Molecule that blocks bone destruction could provide potential therapeutic target for osteoporosis

UT-Southwestern cancer researchers have identified a promising molecule that blocks bone destruction and, therefore, could provide a potential therapeutic target for osteoporosis and bone metastases of cancer.

The molecule, miR-34a, belongs to a family of small molecules called microRNAs (miRNAs) that serve as brakes to help regulate how much of a protein is made, which in turn, determines how cells respond.

UT-Southwestern researchers found that mice with higher than normal levels of miR-34a had increased bone mass and reduced bone breakdown. This outcome is achieved because miR-34a blocks the development of bone-destroying cells called 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 senior author Dr. Yihong Wan, Assistant Professor of Pharmacology and member of the UT-Southwestern Harold C. Simmons Cancer Center.

Her team found that injecting nanoparticles containing an artificial version, or mimic, of miR-34a into a mouse with post-menopausal osteoporosis decreased- bone loss. "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, Virginia Murchison Linthicum Scholar in Medical Research at UT-Southwestern.

The study is published online in the journal Nature.

High levels of bone destruction and reduced bone density caused by excessive osteoclasts are characteristic of osteoporosis, a common bone disease in which bones become fragile and susceptible to fracture. This condition disproportionately affects seniors and women, and leads to more than 1.5 million fractures annually.

miR-34a could have an additional therapeutic application, offering protection from bone metastases in a variety of cancers, Dr. Wan noted. Bone metastases happen when cancer cells travel from the primary tumor site to the bone, establishing a new cancer location. Researchers saw that injecting the miR-34a mimic in mice could prevent the metastasis of breast and skin cancer cells specifically to bone, mainly by disarming the metastatic niche in bone.

Co-author Dr. Joshua Mendell, Professor of Molecular Biology at UT-Southwestern and member of the UT-Southwestern Harold C. Simmons Cancer Center, noted that his laboratory previously showed that miR-34a can directly suppress the growth of cancer cells.

-"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. Mendell, CPRIT Scholar in Cancer Research. CPRIT is the Cancer Prevention and Research Institute of Texas, which provides voter-approved state funds for groundbreaking cancer research and prevention programs and services in Texas.