Researchers in the laboratory of Janet Rubin from the University of North Carolina School of Medicine have discovered that a compound from mold can drive mesenchymal stem cells (MSCs) to become osteoblasts, which are the cells that make bone.
MSCs are found in many different tissues without our bodies, ranging from bone marrow, to fat, to tendons, to liver, muscle, brain, and the heart. MSCs have the ability to readily differentiate into bone, fat, and cartilage, and with a little coaxing in the laboratory, they can also form smooth muscle, blood vessels, and even neurons. The key to using these cells is fine-tuning their differentiation in the clinic to efficiently make one cell type over and above another.
Rubin and her colleagues showed that by treating MSCs with cytochalasin D, the cells overwhelmingly became bone cells (osteoblasts). Furthermore, when cytochalasin D was injected into the bone cavity inside bones, it also triggered the formation of bone.
Rubin commented that the “bone forms quickly. The data and images are so clear; you don’t have to be a bone biologist to see what cytochalasin D does in one week in a mouse.”
Rubin continued: “This is not what we expected. This was not what we were trying to do in the lab. But what we’ve found could become an amazing way to jump-start local bone formation. However, this will not address osteoporosis, which involves bone loss throughout the skeleton.”
Cytochalasins are known to target the major cytoskeletal protein actin. Actin self-assembles to form long chain known as microfilaments, and are involved in such vital cell processes as movement, cell shape, cell extensions, vesicle trafficking, and other essential processes in the cell. Cytochalasins disassemble actin microfilaments, which increases the pool of actin monomers in the cell. Rubin and her team showed that these actin monomers went into the cell nucleus and regulated gene expression. Specifically, they turned on the genes responsible for osteoblasts differentiation.
This a novel use of actin by cells, since actin is not normally known to traffic to the nucleus and affect gene expression.
If Rubin and her group disassembled the actin cytoskeleton but prevented actin from trafficking to the nucleus, the MSCs nerve differentiated into osteoblasts.
Cytochalasin D also worked in live mice to drive the formation of bone.
Because bone formation is largely the same in humans and mice, this research is probably translatable. Even though clinicians may not want to use cytochalasin D in human patients, screening compounds that trigger the transport of monomeric actin into the nucleus might be a good way to induce MSCs to form bone cells.
This work was published in the journal Stem Cells 2015; 33(10:3065.