Vitamin K pathway found to control bone resorption in mice

By AI, Created 3:20 PM UTC, May 19, 2026, /AGP/ – A study in male mice has identified a vitamin K-dependent GAS6 signaling pathway in osteoblasts that helps control osteoclast fusion and bone breakdown. The findings, published April 28, 2026 in Bone Research, could inform future osteoporosis therapies that target excessive bone resorption.

Why it matters: - The study points to a previously unknown way bone-forming cells help control bone breakdown. - The findings could help explain how vitamin K supports skeletal health beyond bone mineralization. - Targeting the GAS6-TAM pathway may offer a future route to treat osteoporosis and other diseases marked by excessive osteoclast activity.

What happened: - A research team led by Dr. Mathieu Ferron at the Montreal Clinical Research Institute studied vitamin K-dependent γ-carboxylation in bone cells. - The work was published April 28, 2026, in Volume 14 of Bone Research. - The study used genetically engineered mice, osteoblast-osteoclast co-cultures, molecular signaling tests, histology and microcomputed tomography imaging.

The details: - The enzymes γ-glutamyl carboxylase and vitamin K oxidoreductase were expressed mainly in osteoblasts, not osteoclasts. - When the team selectively deleted γ-glutamyl carboxylase in osteoblasts of male mice, the animals developed higher bone mass by 6 months of age. - The bone in those mice was denser and more interconnected. - The higher bone mass came mainly from reduced bone resorption, not increased bone formation. - Osteoblast-specific loss of γ-glutamyl carboxylase lowered osteoclast number and surface area. - Circulating markers of bone resorption also declined. - In co-culture experiments, osteoblasts lacking γ-glutamyl carboxylase were less able to support osteoclast formation. - The researchers identified GAS6 as the γ-carboxylated protein linking osteoblasts to osteoclasts. - GAS6 is secreted by osteoblasts and activates the AXL and MerTK receptors on pre-osteoclasts. - Recombinant γ-carboxylated GAS6 increased osteoclast formation and produced larger multinucleated osteoclasts. - Pharmacological inhibition of AXL and MerTK suppressed osteoclast generation. - In transgenic mice with elevated circulating GAS6, bone density fell and osteoclast number rose. - Those mice also showed enhanced bone resorption. - GAS6 mainly promoted fusion of pre-osteoclasts into mature multinucleated osteoclasts rather than changing osteoclast differentiation itself.

Between the lines: - The data suggest vitamin K signaling in bone is not just about building bone matrix. - The pathway appears to work through osteoblast-to-osteoclast communication, which gives researchers a more specific target than broad bone-remodeling approaches. - Dr. Ferron said the findings show osteoblasts actively regulate osteoclast maturation through GAS6 signaling. - Dr. Ferron also said targeting GAS6 or TAM receptor signaling could eventually help reduce excessive bone resorption while preserving normal remodeling.

What’s next: - The GAS6-TAM axis may become a target for future drug development in osteoporosis and related metabolic bone diseases. - Further research will need to test whether the mouse findings translate to human bone biology and clinical treatment. - The original paper was titled “Vitamin K-dependent carboxylation in osteoblasts regulates bone resorption through GAS6 in male mice.” The DOI is 10.1038/s41413-026-00528-2.

The bottom line: - Vitamin K appears to control bone resorption through a specific signaling route in osteoblasts, and GAS6 is the key messenger.