A study published on July 6, 2026, in Bone Research reveals that blocking the Axl receptor tyrosine kinase promotes bone formation. Led by Dr. Mubashir Ahmad at Ulm University, researchers used a kinome-wide RNA interference screen to identify Axl as an osteoblast regulator. Inhibiting Axl with the small-molecule BGB324 increased bone mass and osteocytes in mice without toxicity. This pathway activates interferon-stimulating gene 15 to mature bone-building cells, offering a potential osteoporosis treatment.
Axl receptor blocking osteoporosis
- ▪A study published on July 6, 2026, in the journal Bone Research suggests that blocking the Axl receptor tyrosine kinase may promote bone formation.
- ▪Researchers from Ulm University and Ulm University Hospital identified the Axl receptor as a potential therapeutic target for treating osteoporosis and other bone-related disorders.
Kinome-wide RNAi screening methodology
- ▪Researchers conducted a kinome-wide RNA interference screen of hundreds of protein kinases to identify new regulators of bone formation.
- ▪The kinome-wide RNA interference screen identified the Axl receptor as a previously unrecognized regulator of osteoblasts, the cells responsible for building bone.
BGB324 preclinical bone formation
- ▪Mice treated with the small-molecule Axl inhibitor BGB324 developed greater bone mass in their long bones and vertebrae due to increased bone formation.
- ▪The administration of the Axl inhibitor BGB324 in mice increased the number of osteocytes and was well tolerated without significant toxicity.
Interferon-stimulating gene 15 pathway
- ▪Inhibiting the Axl receptor removed a molecular signal that normally restrains bone-forming cells, allowing them to mature and build bone more effectively.
- ▪Inhibiting the Axl receptor increased the activity of interferon-stimulating gene 15, a protein that helps activate signals needed for osteoblast maturation.
BGB324 existing cancer trials
- ▪The existing clinical trial history of the Axl inhibitor BGB324 could support future research into translating Axl-targeting therapies for osteoporosis.
- ▪The Axl inhibitor BGB324 has been investigated in clinical trials for certain cancers because the Axl receptor plays roles in tumor growth and immune regulation.
Osteoblast maturation molecular mechanisms
- ▪Further clinical research is required to determine whether targeting the Axl receptor can safely and effectively improve bone health in humans.
- ▪Blocking the Axl receptor promoted the maturation of osteoblasts and increased their ability to produce mineralized bone tissue in laboratory models.
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