SEOUL, October 13 (AJP) - A single protein speeds the breakdown of bone and holds back the growth of new bone, researchers at Sookmyung Women's University found in mice. The finding points to a possible new target for osteoporosis treatment.
Bone is rebuilt constantly throughout life. Cells called osteoclasts break down old bone, while cells called osteoblasts lay down new bone.
Healthy bone depends on the two staying in balance. When breakdown outpaces building, bone mass falls, and over time that can lead to osteoporosis, a disease in which bones grow thin and break easily.
The team was led by Yang Young, a professor in Sookmyung's Division of Biological Sciences, and Mun Se-hwan, a professor at the university's Research Institute of Women's Health. It studied β-TrCP2, a protein that marks other proteins for disposal inside cells.
Mice bred without the gene for β-TrCP2 formed fewer bone-destroying cells and broke down less bone. At the same time, their bone-building cells grew more active and made more new bone.
The same pattern held in mice whose ovaries had been removed, a standard model of the bone loss women experience after menopause.
Without β-TrCP2, those mice lost less bone, formed more and ended up with greater overall bone mass.
Removing a closely related protein, β-TrCP1, did not produce the same results, according to the paper.
In bone-forming cells, the missing protein allowed β-catenin, a molecule that switches on bone-building genes, to accumulate.
Experiments on injured bone also showed faster formation of new bone and faster recovery. The team said this points to a possible role in repairing damaged bone, not only in preventing its loss.
"In particular, by confirming an actual bone-improving effect in an animal model of osteoporosis, we presented its potential as a new therapeutic target," Yang said.
Yang said the team plans to develop technology that can regulate β-TrCP2 "safely and selectively." The team also plans to study whether the approach could extend to inflammatory bone-loss diseases such as rheumatoid arthritis.
All of the results come from cell experiments and genetically altered mice. The team did not test a drug. It removed the gene instead, and a treatment that can safely target the protein in people has yet to be developed.
Teams led by Kyung-Hyun Park-Min at Weill Cornell Medicine and Choogon Lee at Florida State University took part in the study.
The paper was published online in September in Arthritis & Rheumatology, the journal of the American College of Rheumatology. Doctoral student Kim Woo-jung was first author, with Yang and Mun as co-corresponding authors.
[Reference Information]
Journal/Source: Arthritis & Rheumatology (IF 9.9, top 6.9% in rheumatology)
Title: Dual Effects of β-TrCP2 Deletion in Bone Homeostasis: Suppression of Osteoclastogenesis and Enhancement of Osteoblast Activity
Link/DOI: https://doi.org/10.1002/art.70351
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