ELMO1 Inhibition as a Basis for Osteoporosis Therapies

Osteoporosis is the name given to the characteristic loss of bone mass and strength that takes place with age. Bone is constantly remodeled, and this condition is the consequence of a growing imbalance between the activity of osteoclasts, responsible for breaking down bone, and osteoblasts, responsible for building bone. Researchers here make the observation that osteoclasts perform functions related to bone construction even as they break down bone, meaning that therapies intended to limit osteoclast populations may not work as well as hoped. Instead, specifically dialing back only the breakdown of bone tissue by altering regulatory proteins in osteoclasts, without dialing back their other activities, may be a better approach.

Scientists are eager to understand what causes the bone loss of osteoporosis, and to develop new ways to treat and prevent it. Researchers have found an important contributor, a cellular protein called ELMO1. This protein, they found, promotes the activity of the bone-removing osteoclasts. While osteoclasts may seem like 'bad guys' because they remove bone, they are critical for bone health, as they normally remove just enough to stimulate new bone growth. The problem arises when the osteoclasts become too aggressive and remove more bone than the body makes. Then bone density suffers and bones grow weaker.

This excessive bone degradation is likely influenced by genetic factors. They note that many of the genes and proteins linked to ELMO1 have been previously associated with bone disorders and osteoclast function. Encouragingly, the researchers were able to prevent bone loss in lab mice by blocking ELMO1, including in two different models of rheumatoid arthritis (RA). That suggests clinicians may be able to target the protein in people as a way to treat or prevent bone loss caused by osteoporosis and RA.

They note that prior efforts to treat osteoporosis by targeting osteoclasts have had only mixed success, and they offer a potential explanation for why: Osteoclasts not only remove bone but play a role in calling in other cells to do bone replacement. As such, targeting ELMO1 may offer a better option than simply waging war on the osteoclasts. "We used a peptide to target ELMO1 activity and were able to inhibit degradation of the bone matrix in cultured osteoclasts without affecting their numbers. We hope that these new osteoclast regulators identified in our study can be developed into future treatments for conditions of excessive bone loss such as osteoporosis and arthritis."

Link: https://www.eurekalert.org/news-releases/931365

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