Bone morphogenetic protein 6 (BMP6) is a protein produced in the human body that functions as a signaling molecule, carrying messages between cells. These signals direct cells to perform specific actions, such as changing their function or multiplying. BMP6 belongs to the transforming growth factor-beta (TGF-β) superfamily, which is involved in cellular growth and development. As a secreted protein, it travels to influence the behavior of target cells throughout the body.
Function in Bone Development
BMP6 is an inducer of osteogenesis, the process of new bone formation. It works by sending signals to mesenchymal stem cells, which are versatile cells that have not yet been assigned a specific function. The signal from BMP6 instructs these stem cells to differentiate, transforming them into osteoblasts—the specialized cells responsible for building bone tissue. This process is necessary during embryonic development for the initial formation of the skeleton.
In adult life, BMP6 is active, contributing to the maintenance and repair of bone tissue. When a bone is fractured, the body’s repair mechanisms are activated, and BMP6 expression is observed throughout the healing process. Its presence helps guide osteoblasts to the injury site, stimulating the creation of new bone matrix to mend the break. The protein enhances the expression of other indicators of bone formation and stimulates the calcification of the cellular matrix, which hardens the new tissue.
The osteogenic capability of BMP6 is high among the different types of bone morphogenetic proteins. This potency is partly due to its resistance to natural inhibitors found in the body, allowing its bone-forming signal to remain effective. This makes it a factor not just in routine bone maintenance but also in more demanding situations like healing significant fractures.
Regulation of Iron in the Body
BMP6 also has a function in managing the body’s iron levels, a primary mechanism for maintaining iron homeostasis. It acts as the regulator of a hormone called hepcidin, which is produced by the liver. Hepcidin is the controller of iron in the bloodstream, and BMP6 is the signal that dictates its production.
The regulatory process begins in the liver’s endothelial cells, which sense the amount of iron in circulation. When iron levels are high, these cells increase their production of BMP6. This secreted BMP6 then acts on nearby liver cells (hepatocytes), initiating a signaling cascade that triggers the transcription of the hepcidin gene and leading to increased production of the hepcidin hormone.
Once released into the bloodstream, hepcidin travels to sites of iron absorption and storage, primarily the small intestine and macrophages in the spleen. It works by blocking the action of ferroportin, the protein that allows iron to exit these cells and enter the blood. By causing the breakdown of ferroportin, hepcidin traps iron inside these cells, preventing both the absorption of dietary iron and the release of recycled iron from old red blood cells. This feedback loop ensures the body does not accumulate toxic levels of iron.
Connection to Disease Processes
Improper BMP6 signaling is linked to several diseases. When BMP6 activity is low, it fails to stimulate hepcidin production, leading to unchecked iron absorption and causing iron overload disorders. Mutations in the BMP6 gene are a cause of hereditary hemochromatosis, a condition of progressive iron accumulation in organs that can lead to significant damage. Patients with these mutations often present with a late-onset, moderate form of the disease.
Disruptions in this pathway are involved in HFE-related hemochromatosis, the most common form of the disorder. Studies in mouse models have shown that a lack of functional HFE protein impairs the BMP6 signaling pathway, resulting in inappropriately low hepcidin levels for the amount of iron in the body. This failure of the body’s iron-sensing mechanism is a factor in the development of the disease.
The role of BMP6 in cancer appears to be context-dependent. In some malignancies, such as prostate cancer, elevated BMP6 levels secreted by cancer cells can promote the spread of tumors to the bone. Conversely, in certain types of breast cancer, BMP6 has been observed to have a tumor-suppressing effect. This dual behavior highlights how the protein’s influence depends on the cellular environment and the specific type of cancer involved.
Therapeutic Applications and Research
Scientists are exploring ways to manipulate BMP6 signaling for medical benefit. In orthopedics, the bone-forming capacity of BMP6 is being harnessed to treat bone injuries. Recombinant human BMP6 (rhBMP6), a lab-manufactured version of the protein, is being developed to stimulate bone regeneration. It can be applied directly to the site of a severe fracture or used to enhance spinal fusion procedures, potentially reducing healing times and improving outcomes.
One approach involves combining rhBMP6 with a patient’s own blood coagulum to create a natural, biocompatible carrier that delivers the protein directly to the injury site. This method has shown promise in clinical trials for accelerating bone healing in wrist fractures and is being investigated for spinal fusion surgeries. The goal of these therapies is to provide an osteoinductive signal precisely where it is needed, minimizing side effects and improving bone repair.
Beyond bone healing, targeting the BMP6-hepcidin pathway is a focus of research for treating iron disorders. For conditions of iron overload like hemochromatosis, therapies that mimic or enhance BMP6 activity could offer a way to restore hepcidin production and control iron levels. Conversely, for certain anemias characterized by high hepcidin, developing drugs that block the BMP6 signal could help release stored iron and improve red blood cell production.