Receptor antagonist reduces age-related bone loss in mice
Bone remodeling involves a regulation between osteoblasts for bone formation and osteoclasts for bone resorption, and this process shifts out of balance with age and with the development of osteoporosis. The complement system, activated as part of the innate immune response to infection, also functions in bone development. The G protein-coupled receptor C3aR is expressed as a component of the complement system in bone marrow cells. Fangyu Li and Shun Cui at Huazhong University of Science and Technology investigated whether C3aR plays a role in age-related impacts on bone remodeling. They published their recent findings in the Journal of Biological Chemistry.
The researchers first noted that C3aR expression trends upward as mice age, in conjunction with higher levels of senescence markers. In contrast, mice with C3aR knocked out showed an increase in bone mass compared to a control group of the same age. The C3aR knockout mice also exhibited higher expression of the osteogenic marker osteoprotegerin and lower expression of the osteoclast marker tartaric acid resistance phosphatase, suggesting a shift toward bone formation over resorption.
In addition, the authors tested a C3aR antagonist, called JR14a, in cells treated with D-galactose to mimic cell damage caused by aging and found that the antagonist restored cell viability. They applied JR14a to a mouse model, and their histologic staining showed an increase in osteoblasts and a decrease in osteoclasts, suggesting partial inhibition of bone loss.
Fluorescence labeling experiments performed in this study indicated that JR14a initiates YAP1/β-catenin signaling, a pathway known to promote osteoblast differentiation. Future studies will help determine the details of downstream effects caused by C3aR inhibition and the possibility of targeting C3aR for relieving age-related dysfunction in bone remodeling.
Enjoy reading ASBMB Today?
Become a member to receive the print edition four times a year and the digital edition monthly.
Learn moreGet the latest from ASBMB Today
Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.
Latest in Science
Science highlights or most popular articles

Mapping the placenta’s hormone network
Study uncovers how the placenta actively metabolizes not only glucocorticoids but also novel androgens and progesterones, reshaping our understanding of pregnancy and its complications.

Biochemists and molecular biologists sweep major 2025 honors
Recent Nobel, MacArthur and Kimberly Prize honorees highlight the power of biochemistry and molecular biology to drive discovery, including immune tolerance, vaccine design and metabolic disease, and to advance medicine and improve human health.

Spider-like proteins spin defenses to control immunity
Researchers from Utrecht University discovered two distinct binding modes of a spider-shaped immune inhibitor found in serum.

A biological camera: How AI is transforming retinal imaging
AI is helping clinicians see a more detailed view into the eye, allowing them to detect diabetic retinopathy earlier and expand access through tele-ophthalmology. These advances could help millions see a clearer future.

AI in the lab: The power of smarter questions
An assistant professor discusses AI's evolution from a buzzword to a trusted research partner. It helps streamline reviews, troubleshoot code, save time and spark ideas, but its success relies on combining AI with expertise and critical thinking.

Training AI to uncover novel antimicrobials
Antibiotic resistance kills millions, but César de la Fuente’s lab is fighting back. By pairing AI with human insight, researchers are uncovering hidden antimicrobial peptides across the tree of life with a 93% success rate against deadly pathogens.