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Inhibition of AXL receptor tyrosine kinase increases osteoblast function and bone mass
Mubashir Ahmad1,2, Christoph Kölbl3, Irfana Jan4,5
1Institute of Molecular Endocrinology and Physiology, Ulm University, Ulm, Germany. ahmad.mubashir@uni-ulm.de.
Bone Research
|July 6, 2026
Summary
Researchers identified AXL receptor tyrosine kinase (Axl) as a target to treat osteoporosis. Inhibiting Axl promotes bone formation, offering a new therapeutic avenue for bone disease.
Area of Science:
- Molecular biology
- Cell biology
- Pharmacology
Background:
- Osteoporosis is a common age-related bone disease with high fracture risk.
- Current treatments use costly biologics, necessitating accessible alternatives.
- Targeting osteoblastogenesis regulators with small molecules is crucial for new therapies.
Purpose of the Study:
- To identify novel regulators of osteoblastogenesis.
- To evaluate AXL receptor tyrosine kinase (Axl) as a therapeutic target for osteoporosis.
Main Methods:
- Unbiased kinome-wide RNAi screen in murine osteoblasts.
- siRNA-mediated knockdown and pharmacological inhibition (BGB324) of Axl.
- In vitro osteoblast differentiation and mineralization assays.
- In vivo bone mass analysis in mice.
- Mechanistic studies involving Isg15 and Erk phosphorylation.
Main Results:
- Axl was identified as a negative regulator of osteoblast differentiation.
- Axl inhibition enhanced osteoblast differentiation and mineralization in vitro.
- BGB324 treatment increased bone mass in mice by promoting bone formation.
- Axl inhibition upregulated Isg15, which is crucial for osteoblast differentiation.
Conclusions:
- AXL receptor tyrosine kinase (Axl) is a promising therapeutic target for osteoporosis.
- Small molecule inhibition of Axl offers a potential treatment strategy for bone disorders.
- The Axl-Isg15-Erk pathway is critical for regulating osteoblast differentiation.
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