BoneKEy Reports | BoneKEy Watch
Therapeutic potential of adding an MSC-specific ligand to alendronate
DOI:10.1038/bonekey.2012.72
A possible strategy to prevent osteoporosis is to reverse the age-related decline in osteogenesis. This study investigates the potential for boosting the population of mesenchymal stem cells (MSCs) in bone marrow so that they differentiate to replenish the supply of osteoblasts.
Guan et al. exploited the integrin α4β1 protein that occurs naturally on the surface of MSCs as the target for a synthetic ligand, LLP2A, itself attached to alendronate (Ale), a bisphosphonate that has high affinity for bone. After showing that this conglomeration induced migration of MSCs and differentiation into osteoblasts in vitro, the researchers then gave immunocompetent mice a single injection of LLP2A-Ale. Treated mice showed a significant increase in bone mass compared to controls given LLP2A only, and exhibited greater vertebral maximum load and enhanced maximum bone stress, indicating superior bone quality as well as quantity.
Treatment of immunodeficient mice with LLP2A-Ale after xenotransplantation resulted in human MSCs within the bone matrix and at the bone surface. Injection of LLP2A-Ale also prevented further loss of trabecular bone mass due to ageing in C57BL/6 mice (osteopenic mice), and partially prevented induced bone loss in ovarectomized mice.
Editor's comment: A synthetic peptidomimetic ligand (LLP2A) can attract endogenous and transplanted MSCs via binding to α4β1 integrin on MSCs. By attaching LLP2A to alendronate, the LLP2A ligand is able to home in on the bone marrow, where it stimulates bone formation. This novel therapeutic strategy may have applications in bone fracture repair as well as osteoporosis.
This work is licensed under a
Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.