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UMKC researchers awarded $8.3 million NIH grant to study 'crosstalk' between bones and muscles

Posted Jul 25, 2012

Interdisciplinary research includes investigators from
Schools of Dentistry, Nursing, Pharmacy and Computing and Engineering

The University of Missouri-Kansas City has received a five-year, $8.3 million grant from the National Institute on Aging, part of the National Institutes of Health, to study the relationship between osteoporosis (loss of bone density) and sarcopenia (loss of muscle mass) as people age. The research will be led by Lynda Bonewald, Ph.D., Curators' Professor and director of the Bone Biology research program at the School of Dentistry, and conducted by a multidisciplinary team of investigators from UMKC's Bone Biology and Muscle Biology research groups, part of the university's Center of Excellence in Dental and Musculoskeletal Tissues.

"Osteoporosis and sarcopenia are major clinical problems in the nation's aging population," said Dr. Bonewald. "In many patients, these two conditions occur concurrently, posing serious health threats for the elderly -- physical instability, susceptibility to falls and consequently to fracture, morbidity, and premature death."

The UMKC research will focus on "endocrine crosstalk," or how bone and muscle cells biochemically communicate with each other in health and disease. While current dogma assumes that the muscle-bone relationship is driven purely by mechanical factors, the UMKC investigators propose that bone can act, in effect, as an "endocrine organ" to control muscle physiology and disease. A reciprocal relationship may also exist between muscle and bone. Therefore, disease in either organ may have negative repercussions on the reciprocal organ through systemic endocrine factors. Dr. Bonewald believes this new line of research could potentially lead to the discovery of new therapeutic interventions for the prevention and treatment of bone and muscle diseases.

The traditional view of skeletal muscle and bone interaction is that skeletal muscle loads bone and bone provides an attachment site for muscle. This mechanical perspective implies that as muscle function declines, this would result in decreased loading of the skeleton and therefore would result in a decrease in bone mass.

"However, muscle atrophy alone cannot fully explain the totality of osteoporosis and, reciprocally, aging associated decreases in bone mass do not fully explain sarcopenia," Dr. Bonewald said.

In collaboration with Dr. Bonewald, other members of the research team includes Mark Johnson, Ph.D., and Sarah Dallas, Ph.D., members of the Bone Biology research group at the School of Dentistry; and Marco Brotto, Ph.D., director of the Muscle Biology research program housed at the School of Nursing. At the UMKC School of Computing and Engineering, investigators Ganesh Thiagarajan, Ph.D., and Amber Rath-Stern, Ph.D., will work with the clinical researchers to develop computer models for measuring, among other things, the impact of muscle loading on bones. William Guthiel, Ph.D., from the UMKC School of Pharmacy will work with Dr. Bonewald to identify these muscle and bone signaling factors.

The ultimate goal of this research is to determine the molecular and cellular mechanisms that contribute to the coordinated development of bone and muscle conditions in the elderly. Current treatments for osteoporosis are aimed at controlling the activity of special cells in bone which are responsible for bone formation and bone removal, called osteoblasts and osteoclasts, respectively.

"However, there is a third cell, called the osteocyte, which is embedded within the mineralized bone matrix and, until recently, has been overlooked. Recent research has shown that these cells are major regulators of the function of osteoblasts and osteoclasts and may play a centralized role in regulating bone mass," said Dr. Dallas.

According to the researchers, one of the more exciting pieces of new evidence they have uncovered is the discovery that, as people age, a factor produced by muscle and which acts on the osteocyte and enhances both its viability and ability to respond to exercise, is no longer being made.

"If we can identify this factor and understand how it alters the osteocyte, then perhaps we can design a drug that will do the same thing, and thereby restore the skeleton to a mass and strength like when we were younger," added Dr. Johnson.

Dr. Bonewald and her colleagues had an opportunity to showcase their research, which has garnered significant national and international attention, to an elite gathering of muscle and bone researchers when the American Society for Bone and Mineral Research hosted a special topical meeting -- Bone and Skeletal Muscle Interactions -- in Kansas City, July 17-18.

"A big part of the reason that ASBMR chose to bring this meeting to Kansas City is because of the unique multidisciplinary nature of the research we are doing here," said Dr. Brotto. "Bringing a meeting like this one to UMKC and Kansas City really puts the UMKC Bone and Muscle research programs at the center of this new, exciting, and very promising research field."