According to the research, AXL receptor tyrosine kinase (Axl) functions as a negative controller of osteoblast differentiation by dampening Erk1/2 phosphorylation and lowering Isg15 levels. Interfering with Axl could counteract these actions, thereby encouraging bone formation and
Scientists pinpoint AXL receptor tyrosine kinase as a crucial controller of bone formation, unveiling a promising novel treatment target for osteoporosis.
SICHUAN, CHINA, July 28, 2026 /EINPresswire.com/ — Osteoporosis impacts countless individuals across the globe, making bones weaker and raising fracture risk. Now, scientists have pinpointed the AXL receptor tyrosine kinase (Axl) as a critical molecule that restrains the activity of bone-forming cells. Using a small-molecule blocker to inhibit Axl led to greater bone formation and increased bone mass in mice, while also clarifying how this receptor governs bone development. These discoveries may pave the way for more affordable therapies for osteoporosis and other skeletal disorders.
Osteoporosis stands as one of the most prevalent age-related bone conditions, affecting millions worldwide and heightening the likelihood of fractures, disability, and diminished quality of life. Although existing treatments can decelerate bone loss or spur new bone growth, many anabolic options depend on biologic drugs that come with high costs and require routine injections. The quest for more accessible therapies that prompt the body to generate new bone continues to be a significant hurdle.
A fresh investigation published online on July 6, 2026, in Volume 14 of the journal Bone Research indicates that blocking Axl—a receptor tyrosine kinase involved in cell signaling—could provide a novel route to stimulate bone formation. The work was carried out by a team led by Dr. Mubashir Ahmad, who launched the project alongside Prof. Dr. Jan Tuckermann from the Institute of Molecular Endocrinology and Physiology at Ulm University, Germany. After finishing his doctorate, Dr. Ahmad pursued the research as a postdoctoral fellow under Prof. Dr. Anita Ignatius at the Institute of Orthopedic Research and Biomechanics, Ulm University Hospital, Germany, in close collaboration with the Tuckermann Lab. The investigators discovered that inhibiting Axl boosts the function of bone-forming cells (osteoblasts) and elevates bone mass in mice. These results underscore Axl as a compelling therapeutic target for osteoporosis and other bone-related conditions.
“Our results highlight Axl as a promising therapeutic target for osteoporosis and other bone-related disorders,” says Dr. Ahmad. “By blocking this receptor, we succeeded in triggering bone formation in preclinical models, laying the groundwork for the development of new anabolic therapies.”
To identify new regulators of bone formation, the researchers first conducted a kinome-wide RNA interference (RNAi) screen—a method that systematically silences genes to reveal their roles. After screening hundreds of protein kinases, they singled out Axl as a previously unrecognized controller of osteoblasts, the cells responsible for constructing new bone. The team subsequently verified these observations by reducing Axl activity through both genetic techniques and a small-molecule inhibitor called BGB324, then assessed its effects in bone-forming cells grown in the lab and in mice.
The outcomes consistently demonstrated that blocking Axl encouraged osteoblast maturation and enhanced their capacity to produce mineralized bone tissue. Mice given BGB324 developed greater bone mass in their long bones and vertebrae due to increased bone formation. The treatment also raised the number of osteocytes, indicating that Axl inhibition supports normal bone development. Notably, the treatment was well tolerated in mice, with no signs of significant toxicity observed throughout the study period.
To grasp how Axl influences bone formation, the researchers examined the underlying molecular pathways. They discovered that blocking Axl increased the activity of interferon-stimulating gene 15, a protein that helped activate signals required for osteoblast maturation. “Put simply, inhibiting Axl removed a molecular signal that typically holds back bone-forming cells, allowing them to mature and build bone more effectively. This newly identified pathway offers fresh insight into how bone formation is regulated,” says Prof. Dr. Tuckermann.
Interestingly, BGB324 has already been tested in clinical trials as a treatment for certain cancers, given that Axl plays key roles in tumor growth and immune regulation. Although the present findings stem from in vitro and in vivo studies, the existence of an already available Axl inhibitor could aid future research into osteoporosis therapies.
“Our study delivers new understanding of the molecular mechanisms that regulate osteoblast differentiation and bone formation,” says Prof. Dr. Ignatius. “Further investigations are needed to determine whether targeting Axl can be developed into a safe and effective treatment for osteoporosis and other bone disorders.”
Taken together, these findings identify Axl as a previously unrecognized regulator of bone formation and suggest that blocking its activity could represent a fresh strategy for treating osteoporosis. Additional clinical research will be necessary to determine whether this approach can safely improve bone health in humans.
Reference
Title of original paper: Inhibition of AXL receptor tyrosine kinase increases osteoblast function and bone mass
Journal: Bone Research
DOI: https://doi.org/10.1038/s41413-026-00554-0
About Ulm University, Germany
Established in 1967, Ulm University holds the distinction of being the youngest university in Baden-Württemberg and has undergone dynamic, successful expansion since its founding. It boasts a notable history as a young institution that serves and partners with the community, all while situated on a green campus. As a central pillar of Science City Ulm, the university acts as a beacon for the region and beyond. Its faculties—Engineering, Computer Science and Psychology, Mathematics and Economics, Medicine, and Natural Sciences—excel in research and are deeply dedicated to student support.
Website: https://www.uni-ulm.de/en/
About Dr. Mubashir Ahmad from Ulm University, Germany
Dr. Mubashir Ahmad obtained his PhD from Ulm University, Germany, under the mentorship of Prof. Dr. Jan Tuckermann. He is currently a postdoctoral researcher in the group of Prof. Dr. Anita Ignatius at the Institute of Orthopedic Research and Biomechanics, Ulm University Hospital. With more than 14 years of research experience, he has authored 19 peer-reviewed articles. His research centers on the molecular mechanisms that regulate bone remodeling, osteoblast differentiation, osteoporosis, mechanotransduction, and fracture healing. By integrating molecular biology, functional genomics, genetically modified mouse models, and high-throughput RNA interference (RNAi) screening, his work aims to uncover novel therapeutic targets for bone diseases.
About Professor Anita Ignatius from Ulm University Hospital, Germany
Professor Dr. Anita Ignatius serves as the Director of the Institute of Orthopedic Research and Biomechanics at Ulm University Hospital, Germany. Her research focuses on the regeneration of musculoskeletal tissues, skeletal biomechanics, bone mechanobiology, biomaterials, and tissue engineering, with a particular emphasis on bone defect healing and trauma research. She leads a multidisciplinary team investigating the regeneration of bone, cartilage, ligaments, and intervertebral discs. Professor Ignatius currently heads the Transdisciplinary Centre of Trauma Research at Ulm University and co-directs the Collaborative Research Centre on “Danger Response, Disturbance Factors and Regenerative Potential after Acute Trauma.”
About Professor Jan Tuckermann from Ulm University, Germany
Professor Dr. Jan Tuckermann holds a professorship at the Institute of Molecular Endocrinology and Physiology, Ulm University, Germany. He earned his PhD in Transcriptional Regulation from the German Cancer Research Center and the University of Karlsruhe (KIT), Germany. His research interests encompass nuclear receptors, immune metabolism, bone diseases, osteoimmunology, inflammation resolution, and metabolism. He has served as the Study Dean of Biological Studies at Ulm University and as the President of the German Society for Endocrinology (DGE), contributing to research and education in endocrinology.
Funding information
This work was supported by grants from Deutsche Forschungsgemeinschaft (DFG) to Jan Tuckermann, Anita Ignatius, and Francesco Roselli within the framework of the Collaborative Research Center CRC1149 “Danger Response, Disturbance Factors and Regenerative Potential after Trauma” (Project No. 251293561– CRC1149, INST 40/492-3), and a DFG grant to Jan Tuckermann within the framework of Collaborative Research Center CRC1506 “Aging at interfaces” (Project No. 450627322) and Transregio TRR 369 DIONE “Degeneration of bone due to Inflammation” (Project No. 501752319). Francesco Roselli and Burak Özkan were also supported by the BMBF through the JPND program within the DC4MND consortium (grant no. BMBF 01ED2301). Additional funding was provided by the Federal Ministry of Research, Technology and Space (Bundesministerium für Forschung, Technologie und Raumfahrt, BMFTR) as part of the German Center for Child and Adolescent Health (DZKJ) under the funding code 01GL2407A. Mubashir Ahmad was supported by a Baustein grant (L.SBN.0224) from the Medical Faculty of Ulm University. Open Access funding enabled and organized by Projekt DEAL.
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